bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunohistochemistry for PRAME in Dermatopathology
Authors: Lezcano Cecilia , Jungbluth Achim A. , Busam Klaus J.
Published: October 2023

Preferentially expressed antigen in melanoma (PRAME) is a tumor-associated antigen first identified in a melanoma patient and found to be expressed in most melanomas as well as in variable levels in other malignant neoplasms of epithelial, mesenchymal, or hematolymphoid lineage. Detection of PRAME expression in formalin-fixed paraffin-embedded tissue is possible by immunohistochemistry (IHC) with commercially available monoclonal antibodies. In situ and invasive melanoma frequently show a diffuse pattern of nuclear PRAME immunoreactivity which contrasts with the infrequent and typically nondiffuse staining seen in nevi. In many challenging melanocytic tumors, results of PRAME IHC and other ancillary tests correlate well, but not always: The tests are not interchangeable. Most metastatic melanomas are positive for PRAME, whereas nodal nevi are not. Numerous studies on PRAME IHC have become available in the past few years with results supporting the value of PRAME IHC as an ancillary tool in the evaluation of melanocytic lesions and providing insights into limitations in sensitivity and specificity as well as possible pitfalls that need to be kept in mind by practicing pathologists.
Patterns of Marijuana Use and Nicotine Exposure in Patients Seeking Elective Aesthetic Procedures
Authors: Lu Yi-Hsueh , Mahajan Lakshmi , Rudy Hayeem , Pettitt Brian , Pothula Aravind , Ricci Joseph A.
Published: October 2023

Background:

With the increasing legalization and popularity of marijuana, it is frequently and sometimes unintentionally combined with nicotine-containing products. As a consequence, patients may fail to accurately report usage during preoperative examinations or remain unaware of the inclusion of nicotine. This poses a challenge for clinicians in identifying preoperative nicotine exposure. This study aimed to establish normative data on the use of marijuana and nicotine in plastic surgery patients and correlate it with urine nicotine and cotinine levels.

Methods:

All consecutive patients presenting to the authors’ clinic seeking elective procedures were identified. Patients were surveyed on marijuana and nicotine use, and provided a urine sample for analysis. The survey responses, urine results, surgical treatments, and clinical outcomes were followed up prospectively.

Results:

A total of 135 patients completed the survey and were categorized as nonusers (50%), active nicotine users (19%), active marijuana users (7%), active users of both (13%), or past users (11%). Marijuana users who denied nicotine use showed significantly elevated nicotine and cotinine levels compared with nonusers (average nicotine level, 23.1 ± 13.5 ng/mL [P = 0.00007]; average cotinine level, 221.2 ± 141.8 ng/mL [P = 0.0002]). Fewer than a third of active marijuana or nicotine users reported active use of these products during clinical encounters. There was no difference in urine levels, reported use, or other patient characteristics in patients with and without postoperative complications.

Conclusion:

This is the first descriptive study to document elevated urine nicotine levels in self-reported marijuana users in an urban, diverse patient population seeking elective plastic surgery procedures.
Development of a Psychological Scale for Measuring Disruptive Clinician Behavior
Authors: Fujimoto Manabu , Shimamura Mika , Miyazaki Hiroaki , Inaba Kazuto
Published: October 2023

Objectives

Disruptive clinician behavior worsens communication, information transfer, and teamwork, all of which negatively affect patient safety. Improving safety in medical care requires an accurate assessment of the damage caused by disruptive clinician behavior. Psychometric scales complement case reports, but existing scales have significant limitations. Therefore, this study developed a psychometric scale based on the psychological paradigm to assess disruptive clinician behavior.

Methods

The scale was developed through a sequence of steps. First, we used an open-ended questionnaire targeting 712 nurses, content analysis, and content validity assessment by 5 experts to determine valid items for disruptive clinical behavior. Next, an Internet questionnaire survey targeting 1000 health care staff, exploratory factor analysis, and subfactor analysis was conducted to identify necessary and sufficient factors. Then, we calculated difficulty level and discriminative power. We also conducted a field questionnaire survey targeting 84 staff in a hospital. Finally, we calculatedωcoefficients and then used confirmatory factor analysis to verify the fit of the hypothesized model.

Results

Our open-ended survey involving 478 nurses identified 47 codes in 9 categories. The questionnaire survey involving hospital 1000 medical staff identified 6 factors, with 1 factor subdivided into 4 subfactors and 1 into 2 subfactors. The goodness of fit of the hypothesized 10-factor models with factor pairs and groups was confirmed.

Conclusions

We developed a psychometric scale measuring subjective assessments of harm covering various disruptive clinician behaviors. The scale complements interviews and case reports by generating valid, reliable scores for various disruptive clinician behaviors in health care institutions.
Non-Negative Matrix Factorization for Analyzing State Dependent Neuronal Network Dynamics in Calcium Recordings
Authors: Carbonero Daniel , Noueihed Jad , Kramer Mark A , White John A
Published: October 2023

Calcium imaging allows recording from hundreds of neurons in vivo with the ability to resolve single cell activity. Evaluating and analyzing neuronal responses, while also considering all dimensions of the data set to make specific conclusions, is extremely difficult. Often, descriptive statistics are used to analyze these forms of data. These analyses, however, remove variance by averaging the responses of single neurons across recording sessions, or across combinations of neurons, to create single quantitative metrics, losing the temporal dynamics of neuronal activity, and their responses relative to each other. Dimensionally Reduction (DR) methods serve as a good foundation for these analyses because they reduce the dimensions of the data into components, while still maintaining the variance. Non-negative Matrix Factorization (NMF) is an especially promising DR analysis method for analyzing activity recorded in calcium imaging because of its mathematical constraints, which include positivity and linearity. We adapt NMF for our analyses and compare its performance to alternative dimensionality reduction methods on both artificial and in vivo data. We find that NMF is well-suited for analyzing calcium imaging recordings, accurately capturing the underlying dynamics of the data, and outperforming alternative methods in common use.
Far-reaching displacement effects of artificial light at night in a North American bat community
Authors: Seewagen Chad L. , Nadeau-Gneckow Julia , Adams Amanda M.
Published: October 2023

Artificial light at night (ALAN) is a global pollutant that disrupts circadian rhythmicity and a broad range of physiological processes and behaviors in animals. However, ALAN sensitivity can vary greatly even among closely related species and urgently needs study for much of the world’s nocturnal wildlife, including bats. While an increasing number of bat species have been assessed for light tolerance in recent years, the spatial extent of ALAN’s influence on bats has received little attention. This information need is a barrier to the protection of bats from ALAN in land-use planning and policy, and the development of best practices that effectively buffer bat habitat from light trespass. To help address this information gap for North America, we experimentally tested the distances up to which ALAN affects presence and activity of light-averse little brown bats (Myotis lucifugus) and big brown bats (Eptesicus fuscus), and the composition of a foraging bat assemblage in Connecticut, USA. We used three residential-scale, white, LED floodlights to expose bat foraging habitat to ALAN and compared acoustic activity of bats at distances of 0, 25, 50, and 75 m from the lights between nights when the lights were on versus off. Little brown bats were present on significantly fewer light than dark nights at every distance. Lighting significantly reduced little brown bat activity overall and at the farthest location from the lights (75 m), where it was only 43% of dark-night activity despite 0 lx of illuminance. Presence of big brown bats was not significantly affected at any distance. Big brown bat activity on light nights averaged 48-75% of dark-night activity at each distance but was significantly lower only at 0 m. Community composition on dark and light nights had an average dissimilarity of 38% and significantly differed at 0 m and 25 m. We conclude the type of ALAN used in our study has a disturbance radius of at least 75 m for the little brown bat and up to 25 m for the big brown bat, with a resulting influence on community composition for up to 50 m. Cumulative habitat loss for the imperiled little brown bat caused by ALAN could therefore be substantial. We urge planners and natural resources regulators to consider these footprints when evaluating indirect impacts to bat habitat from current and future sources of ALAN across these species’ ranges.
Deconvolution of Nascent Sequencing Data Using Transcriptional Regulatory Elements
Authors: Maas Zachary , Sigauke Rutendo , Dowell Robin
Published: October 2023

The problem of microdissection of heterogeneous tissue samples is of great interest for both fundamental biology and biomedical research. Until now, microdissection in the form of supervised deconvolution of mixed sequencing samples has been limited to assays measuring gene expression (RNA-seq) or chromatin accessibility (ATAC-seq). We present here the first attempt at solving the supervised deconvolution problem for run-on nascent sequencing data (GRO-seq and PRO-seq), a readout of active transcription. Then, we develop a novel filtering method suited to the mixed set of promoter and enhancer regions provided by nascent sequencing, and apply best-practice standards from the RNA-seq literature, usingin-silicomixtures of cells. Using these methods, we find that enhancer RNAs are highly informative features for supervised deconvolution. In most cases, simple deconvolution methods perform better than more complex ones for solving the nascent deconvolution problem. Furthermore, undifferentiated cell types confound deconvolution of nascent sequencing data, likely as a consequence of transcriptional activity over the highly open chromatin regions of undifferentiated cell types. Our results suggest that while the problem of nascent deconvolution is generally tractable, stronger approaches integrating other sequencing protocols may be required to solve mixtures containing undifferentiated celltypes.
Revealing Molecular Mechanisms of Early-Onset Tongue Cancer by Spatial Transcriptomics
Authors: Patysheva Marina R. , Kolegova Elena S. , Khozyainova Anna A. , Prostakishina Elizaveta A. , Menyailo Maxim E. , Larionova Irina V. , Kovalev Oleg I. , Zavyalova Marina V. , Fedorova Irina K. , Kulbakin Denis E. , Polyakov Andrey P. , Yakovleva Liliya P. , Kropotov Mikhail A. , Sukortseva Natalya S. , Lu Yusheng , Jia Lee , Arora Rohit , Choinzonov Evgeny L. , Bose Pinaki , Denisov Evgeny V.
Published: October 2023

Tongue cancer at a young age demonstrates an increase in incidence, aggressiveness, and poor response to therapy. Classic etiological factors for head and neck tumors such as tobacco, alcohol, and human papillomavirus are not related to early-onset tongue cancer. Mechanisms of development and progression of this cancer remain unclear. In this study, we performed spatial whole-transcriptome profiling of tongue cancer in young adults compared with elderly patients. Oxidative stress, vascular mimicry, and MAPK and JAK-STAT pathways were enriched in early-onset tongue cancer. Tumor microenvironment demonstrated increased gene signatures corresponding to myeloid-derived suppressor cells, tumor-associated macrophages, and plasma cells. The invasive front was accompanied by vascular mimicry with arrangement of tumor-associated macrophages and aggregations of plasma cells and lymphocytes organized into tertiary lymphoid structures. Taken together, these results indicate that early-onset tongue cancer has distinct spatial transcriptomic features and molecular mechanisms compared to older patients.

HIGHLIGHTS

Early-onset tongue cancer demonstrates extremely downregulated oxidative phosphorylation and upregulated glycolysis.

MAPK pathway is the key player in the pathogenesis of tongue cancer in young adults.

Early-onset tongue cancer is characterized by JAK-STAT dependent vascular mimicry supported by tumor-associated macrophages at the invasive edge.

Tongue cancer microenvironment in young adults enriches for immunosuppressive myeloid derived suppressor cells and demonstrates reduced antigen presentation function.

The tumor border in early-onset tongue cancer is enriched with plasma cells and lymphocytes in tertiary lymphoid structures.
Metabolic constraints on growth explain how developmental temperature scales synaptic connectivity relevant for behaviour.
Authors: Züfle Pascal , Batista Letícia L. , Brandão Sofia C. , D'Uva Giovanni , Christian Daniel , Martelli Carlotta
Published: October 2023

Environmental temperature dictates the developmental pace of poikilothermic animals. InDrosophila, brain development at lower temperature is not only slower, but it also results in different wiring outcomes. A first-principle model that imposes different metabolic constraints for the growth of the neural system and the organism explains these findings, predicts brain wiring under ecologically relevant temperature cycles and explains the non-uniform scaling of neural development across temperatures. Dissecting the circuit architecture and function of first, second and third order neurons in the olfactory system, we demonstrate that the consequences of temperature are contingent upon the availability of synaptic partners in different circuits. Despite synaptic scaling, second order neurons encode robust odor representations, while temperature dependent connectivity of third order neurons leads to differences in odor-driven behavior. Therefore some circuit specific developmental programs have evolved to support functional robustness with respect to environmental temperature, while others allow phenotypic plasticity with possible adaptive advantages.
MARK3-mediated Slingshot-1 phosphorylation is essential for polarized lamellipodium formation
Authors: Mishima Toshiaki , Ohta Yusaku , Ohashi Kazumasa , Mizuno Kensaku
Published: October 2023

Cofilin acts as a key regulator of actin cytoskeletal remodeling via stimulating actin filament disassembly. Cofilin is inactivated by Ser-3 phosphorylation and reactivated by cofilin-phosphatase Slingshot-1 (SSH1). SSH1 is activated upon binding to F-actin, and this activation is inhibited by its phosphorylation at Ser-937 and Ser-978 and the subsequent binding of 14-3-3 proteins. In this study, we identified MARK3 (also named Par-1a and C-TAK1) as a kinase responsible for Ser-937/Ser-978 phosphorylation of SSH1. MARK3-mediated phosphorylation promoted SSH1 binding to 14-3-3 proteins and suppressed its F-actin-assisted cofilin-phosphatase activity. When Jurkat cells were stimulated with SDF-1α, actin filaments formed multidirectional F-actin-rich lamellipodia around the cells in the initial stage, and thereafter, they were rearranged as a single polarized lamellipodium to the direction of cell migration. Upon SDF-1α stimulation, SSH1 was translocated into F-actin-rich lamellipodia, but its Ser-937/Ser-978 non-phosphorylatable mutant SSH1(2SA) was retained at the location of the original cortical F-actin. Knockdown of MARK3 or overexpression of SSH1(2SA), similar to SSH1 knockdown, impaired the conversion of multiple lamellipodia to a single polarized lamellipodium. These results indicate that MARK3-mediated Ser-937/Ser-978 phosphorylation is required for SSH1 liberation from F-actin and translocation to lamellipodia, and hence, facilitates the formation of a single polarized lamellipodium for directional cell migration. Our results suggest that the phosphorylation-dephosphorylation cycle of SSH1 is crucial for its localization to lamellipodia via promoting the dissociation-reassociation cycle of SSH1 to F-actin, and thereby the stimulus-induced lamellipodium formation to the direction of cell movement.
Plakins are involved in the maintenance of epithelial polarity
Authors: Geay Juliana , Margaron Yoran , Gentien David , Reyal Fabien , Puisieux Alain , Blanchoin Laurent , Guyon Laurent , Théry Manuel
Published: October 2023

As epithelia are the interface between the organism and the external environment, they are often subject to damage and must be frequently renewed. However, maintaining epithelial integrity during this renewal is challenging, and loss of cell polarity is a potent inducer of tumorigenesis. In this study, we used transcriptomic data from breast cancer cells at different stages of tumor development to identify molecular changes associated with the early stages of tumor transformation. We correlated these protein expression profiles with either cell polarity defects or cell progression along the epithelial-to-mesenchymal transition (EMT). We identified plakins, namely epiplakin (EPPK1), desmoplakin (DSP) and periplakin (PPL), that were downregulated in cells that had lost their epithelial polarity and also downregulated in cells that had progressed through EMT. We further tested them experimentally by knocking down their expression in a non-tumorigenic epithelial breast cell line (MCF10A). We demonstrated their causal role in the loss of polarity, as revealed by the misorientation of the nuclear centrosome vector. We also found that vimentin, a marker of EMT, was overexpressed in plakin knocked-down cells, suggesting that plakins may have both a structural and a regulatory role in maintaining the epithelial state.
The effect of human educational capital on health entitlement acquisition among migrant workers in China: evidence from the 2018 China Migrants Dynamic Survey
Authors: Chen Hong , Chen Chien-Ping , Jin Wang , Wang Yangyang , Qin Lijian
Published: October 2023

Purpose

This paper employs nationwide, large-scale field survey data to provide the first empirical evidence on the impact of human educational capital on the acquisition of health entitlement among Chinese migrant workers. The findings of this study hold significant practical implications for the formulation of policies aimed at improving the health protection of migrant workers, as well as for socioeconomic policies during China's transitional period.

Design/methodology/approach

Using the IVProbit model, this research examines how human educational capital influences the attainment of health entitlement among migrant workers in China by analyzing the impact and mechanism of education on health entitlement. The study is based on the China Migrants Dynamic Survey (CMDS) data from 2018, which include 100,177 observations.

Findings

For migrant workers in China, higher levels of education have a significant positive effect on the acquisition of health entitlements, including medical insurance, health records and health education. The positive impact of human educational capital on health entitlements is more significant for non-provincial cities and young-generation migrant workers. The results also show that human educational capital can influence the acquisition of health entitlements through mediators such as financial status, social integration and health status.

Originality/value

This study represents the first empirical attempt to evaluate the influence of human educational capital on the access of migrant workers in China to health rights and interests. Additionally, the study develops a theoretical framework to examine how the impact of human educational capital varies across migrant workers with different characteristics and their access to health entitlements.
Big ideas, soft governance: managing large-scale school improvement at the national agency level in Sweden
Authors: Nordholm Daniel , Adolfsson Carl-Henrik
Published: October 2023

Purpose

Using a large-scale school improvement program in Sweden as a case, this article aims to explore the state governance of a large-scale school improvement program in Sweden and how officials at the state agency level made sense of the reform ideas and operationalized them in policy actions.

Design/methodology/approach

Data were integrated from Swedish Government Official Reports and formal directives from the Ministry of Education. Officials of the Swedish National Agency for Education (SNAE) were also interviewed. Data were analyzed to identify how regulatory rules, professional norms and cultural–cognitive beliefs shaped SNAE's design of the program.

Findings

The article shows how different types of governance (i.e. regulatory rules, professional norms and cultural–cognitive beliefs) set the direction for managing large-scale school improvement. In particular, in the studied case, the lack of clear regulatory directives enabled sensemaking processes clearly influenced by normative ideas and cultural–cognitive beliefs.

Research limitations/implications

The findings are mostly presented from the perspective of managers, so further study is required to attain a broader understanding of the state agency level's role and function.

Practical implications

By illustrating the strengths of understanding various dimensions of educational governance, the findings are highly relevant to both policymakers and educational managers at different levels of school systems.

Originality/value

The article offers a valuable perspective on large-scale school improvement and educational governance by focusing on a level that has hitherto received little attention.
Study trips: an essential educational component for the training of agribusiness managers
Authors: Islas-Moreno Asael , Uriza-Ávila Daniel Emigdio , Guzmán-Elizalde Ana Lieseld , Aguirre-Álvarez Gabriel
Published: October 2023

Purpose

The study aims to analyze the effect of the previous preparation and the work carried out in the field during a study trip on the development of competencies in agribusiness students.

Design/methodology/approach

The destination was the pineapple area of the Papaloapan Lower Basin in Mexico, and 42 students from 6 different semester levels participated. The students answered a test prior to the trip, received an evaluation for their activities in the field and prepared reports and posters as products of the experience. The relationship between the scores obtained was examined through a comparative analysis.

Findings

The findings are framed in the cyclical model of experiential learning with four stages (feeling, watching, thinking and doing) by Kolb (1984). It is found that the acquisition of specific knowledge about what the experience will entail leads to better preparation, motivation and confidence to live the experience (potentiation of feeling and watching). In turn, specific knowledge and better use of experience promote the development of problem solving, interpersonal and communication skills (potentiation of thinking and doing).

Research limitations/implications

Statistical representativeness is not a quality of the study since it is based on a comparative analysis.

Originality/value

The study analyzes an educational component of great value in the business area, about which little is known in the agribusiness subarea.
Digital service innovation challenges faced during servitization: a multi-level perspective
Authors: Burton Jamie , Story Victoria Mary , Zolkiewski Judy , Nisha Nazifa
Published: October 2023

Purpose

Digital Service innovation (DSI) plays a fundamental role in the successful transition from product manufacturer or traditional service provider to a provider of digitally-enabled service solutions. Multiple impediments make managing this transformation using digital technologies difficult for firms, their customers and wider ecosystems. Extant knowledge of these digital technology impediments requires synthesizing and mapping.

Design/methodology/approach

A systematic literature review (SLR) was conducted. DSI tools and terminology are synthesized via thematic analysis. Subsequently, impediments to DSI for servitization (covering barriers, challenges and tensions) faced by actors across three key innovation phases: strategic planning, design planning and implementation, and four interaction levels (Micro, Meso, Macro-environment, Macro-ecosystem) are mapped via template analysis.

Findings

Six impediment categories (external environmental factors, internal firm factors, capabilities, business models and processes, value creation and interaction) encompassing 28 unique impediment types to DSI during servitization are identified. A framework enabling impediment comparison across innovation phases and ecosystem/network interaction levels, revealing that the majority of barriers can be framed as “challenges” was developed.

Originality/value

Whilst literature is emerging relating to digital servitization, there is a lack of research on the role DSI plays in facilitating digital servitization and no comprehensive study of DSI impediments exists. Additionally, consensus around the cross-disciplinary terminologies used is lacking. This study is a structured attempt to map the domain, summarizing the terms, identifying and clarifying impediment categories and providing recommendations for researchers and managers in tackling the latter.
A Tale of Two Annies: Historical Memory, Archives and the Perpetuation of the Sinners to Angels Trope in American Sex Worker History
Authors: Barnes‐Gilbert Ashley
Published: October 2023

As a historian of sex work, I analyse the power dynamics in the archiving practices and interpretation of sex worker lives, deconstructing the historic and current discourses shaping the possibilities for sex workers. In this article, I explore the legends of nineteenth‐century Madams Annie Cook and Annie Chambers. According to the remaining historical record, Cook and Chambers transformed from sinners to angels prior to death – using sacrifice to eschew their lives of alleged immorality – and in the process, became worthy of historical remembrance and archiving. In recognising the politics of archiving certain documents but not others, I deconstruct the histories of Cook and Chambers to show how discourse and historical memory function to simplify sex worker lives. These tropes serve a larger purpose of constructing white sex worker lives as redeemable and valuable and Black sex workers as unworthy of historical memory, shaping not only the history of sex work but also current debates about sex worker lives, sex trafficking, legal rights and belonging.
Creating a space for trans self‐narrative in 1930s Turkey: Kenan Çinili's memoir
Authors: Sarıtaş Ezgi
Published: October 2023

The memoir of Kenan Çinili, a transgender person who was widely covered by newspapers in Turkey in the second half of the 1930s, sheds light on the historically and geographically unique workings of cisheteronormativity. Through a self‐reflexive reading of the memoir and newspaper accounts from this period, this article explores how a narrative transgender subjectivity emerges from the appropriation and negotiation of tropes, figures and discourses that make this subjectivity intelligible. Through the use of the medium of photography, which exposed and spectacularised gender nonconformity, Kenan was able to performatively embody and visually present a masculine gender identity. However, the space Kenan created for narrative and visual self‐constitution was conditioned by their privileges based on class, urban–rural hierarchy, ethnicity and normative sexual dimorphism.
COVID‐19 vaccine hesitancy in rural and metropolitan Western Australia: A mid‐rollout cross‐sectional analysis of why it exists and potential solutions
Authors:   STRIVE WA Collaborative, Damianopoulos Nicholas , Leigh James , Pugliese Matthew , Frayne Jacqueline , Richards Toby
Published: October 2023

Introduction

Vaccine hesitancy represents a state of uncertainty before a decision about vaccination is made. It can lead to limited vaccine uptake despite adequate supply and an efficacious product. Western Australia (WA) presents a unique challenge with a population widely spread across metropolitan and rural sites and diverse opinions regarding vaccination.

Objective

To elicit and compare the common COVID‐19 vaccine concerns in rural and metropolitan WA, and to identify proposed solutions to vaccine hesitancy.

Design

A voluntary online survey was distributed via social media over a 2‐week period in August 2021 during Phase 2A of the National COVID‐19 Vaccine Rollout Strategy. General practitioners and members of the public living in rural and metropolitan WA over the age of 18 were surveyed regarding COVID‐19 vaccine concerns (blood clots; long‐ and short‐term side effects; lack of testing; and other concerns) and suggested methods to address vaccine hesitancy. Data were analysed with a sequential mixed methods and thematic analysis approach.

Findings

There were 468 general population respondents to our survey, of whom 19.0% (n = 89) lived rurally. A majority (52.6% [n = 246]) of general respondents expressed concerns about COVID‐19 vaccine safety. The commonest concerns were long‐ and short‐term side effects, blood clots and inadequate testing. There was a positive correlation between rurality and vaccine concerns; an inverse relationship between rurality and vaccine uptake; and an inverse relationship between vaccine concerns and uptake. Improved media coverage was the commonest solution suggested to address COVID‐19 vaccine hesitancy.

Discussion

A significant proportion of respondents had concerns about vaccine safety; concerns were more common in rural respondents. Rural communities may benefit from location‐targeted media campaigns with a focus on breaking down barriers specific to these members of the population. Vaccine access is more challenging, and consistent messaging from trusted sources is of utmost importance to improve uptake.

Conclusion

COVID‐19 vaccine hesitancy is more common in rural populations. Targeted media‐based education regarding vaccine safety may improve COVID‐19 vaccine uptake.
Triple targeting of RSK, AKT, and S6K as pivotal downstream effectors of PDPK1 by TAS0612 in B‐cell lymphomas
Authors: Katsuragawa‐Taminishi Yoko , Mizutani Shinsuke , Kawaji‐Kanayama Yuka , Onishi Akio , Okamoto Haruya , Isa Reiko , Mizuhara Kentaro , Muramatsu Ayako , Fujino Takahiro , Tsukamoto Taku , Shimura Yuji , Taniwaki Masafumi , Miyagawa‐Hayashino Aya , Konishi Eiichi , Kuroda Junya
Published: October 2023

B‐cell lymphomas (BCLs) are the most common disease entity among hematological malignancies and have various genetically and molecularly distinct subtypes. In this study, we revealed that the blockade of phosphoinositide‐dependent kinase‐1 (PDPK1), the master kinase of AGC kinases, induces a growth inhibition via cell cycle arrest and the induction of apoptosis in all eight BCL‐derived cell lines examined, including those from activated B‐cell‐like diffuse large B‐cell lymphoma (DLBCL), double expressor DLBCL, Burkitt lymphoma, and follicular lymphoma. We also demonstrated that, in these cell lines, RSK2, AKT, and S6K, but not PLK1, SGK, or PKC, are the major downstream therapeutic target molecules of PDPK1 and that RSK2 plays a central role and AKT and S6K play subsidiary functional roles as the downstream effectors of PDPK1 in cell survival and proliferation. Following these results, we confirmed the antilymphoma efficacy of TAS0612, a triple inhibitor for total RSK, including RSK2, AKT, and S6K, not only in these cell lines, regardless of disease subtypes, but also in all 25 patient‐derived B lymphoma cells of various disease subtypes. At the molecular level, TAS0612 caused significant downregulation of MYC and mTOR target genes while inducing the tumor suppressor TP53INP1 protein in these cell lines. These results prove that the simultaneous blockade of RSK2, AKT, and S6K, which are the pivotal downstream substrates of PDPK1, is a novel therapeutic target for the various disease subtypes of BCLs and line up TAS0612 as an attractive candidate agent for BCLs for future clinical development.
Follow‐up care and support to parents of premature children: Multidisciplinary versus regular follow‐up care
Authors: Bouwmeester Daniëlle , Anolda Naber Fabiënne Bertina , Heyman Hiltje , Hoffmann‐Haringsma Angelique , Lens Annick , Brunt Tibor Markus
Published: October 2023

Background

Preterm care involves clinical measures almost exclusively aimed at keeping the preterm alive and ready for discharge from hospital. Children are then enrolled in clinical follow‐up care after this stressful period, but mental or specialised care for parents and child is often not embedded in the routine of a neonatal hospital ward and the family is then dependent on institutions for mental health or child health clinics, that is, regular care that is regionally scattered. This study aimed to investigate experiences of parents with regular care and compare them with parents visiting a fixed, specialised, multidisciplinary institute, outside the hospital walls, for preterm follow‐up care.

Methods

A survey was conducted among 56 parents (regular follow‐up care N = 26; multidisciplinary follow‐up care N = 30) of children born prematurely. The survey consisted out of items like parents' experiences with follow‐up care, like the organisation of care, supportive care, environmental support and experienced stress.

Results

Parents receiving multidisciplinary follow‐up care reported higher levels of satisfaction with organisation of care (F = 5.45; p = 0.023) and supportive care (F = 11.69; p = 0.001) than parents receiving regular follow‐up care. Also, it was found that the extent of support from the social environment alleviated stress but only in parents receiving regular follow‐up care (ß = −0.47; p = 0.016).

Conclusions

The current study findings indicate that experience with follow‐up care is valued higher when receiving multidisciplinary care than regular care, and the degree in environmental support alleviates stress in parents receiving regular care.
Role of SIRT1 in sepsis‐induced encephalopathy: Molecular targets for future therapies
Authors: Shehata Alaa H. , Anter Aliaa F. , Ahmed Al‐Shaimaa F.
Published: October 2023

Sepsis induces neuroinflammation, BBB disruption, cerebral hypoxia, neuronal mitochondrial dysfunction, and cell death causing sepsis‐associated encephalopathy (SAE). These pathological consequences lead to short‐ and long‐term neurobehavioural deficits. Till now there is no specific treatment that directly improves SAE and its associated behavioural impairments. In this review, we discuss the underlying mechanisms of sepsis‐induced brain injury with a focus on the latest progress regarding neuroprotective effects of SIRT1 (silent mating type information regulation‐2 homologue‐1). SIRT1 is an NAD+‐dependent class III protein deacetylase. It is able to modulate multiple downstream signals (including NF‐κB, HMGB, AMPK, PGC1α and FoxO), which are involved in the development of SAE by its deacetylation activity. There are multiple recent studies showing the neuroprotective effects of SIRT1 in neuroinflammation related diseases. The proposed neuroprotective action of SIRT1 is meant to bring a promising therapeutic strategy for managing SAE and ameliorating its related behavioural deficits.
Contemporary changes in phenotypic variation, and the potential consequences for eco‐evolutionary dynamics
Authors: Sanderson Sarah , Bolnick Daniel I. , Kinnison Michael T. , O'Dea Rose E. , Gorné Lucas D. , Hendry Andrew P. , Gotanda Kiyoko M.
Published: October 2023

Most studies assessing rates of phenotypic change focus on population mean trait values, whereas a largely overlooked additional component is changes in population trait variation. Theoretically, eco‐evolutionary dynamics mediated by such changes in trait variation could be as important as those mediated by changes in trait means. To date, however, no study has comprehensively summarised how phenotypic variation is changing in contemporary populations. Here, we explore four questions using a large database: How do changes in trait variances compare to changes in trait means? Do different human disturbances have different effects on trait variance? Do different trait types have different effects on changes in trait variance? Do studies that established a genetic basis for trait change show different patterns from those that did not? We find that changes in variation are typically small; yet we also see some very large changes associated with particular disturbances or trait types. We close by interpreting and discussing the implications of our findings in the context of eco‐evolutionary studies.
Health benefits valuation in three‐generation households—the role of reciprocity
Authors: Bartczak Anna , Budziński Wiktor , Nicińska Anna , Starzykowska Natalia
Published: October 2023

Objective

This study investigates preferences for family resource allocation on health in three‐generation families and examines whether reciprocity attitudes influence preferences and willingness to pay (WTP) for reducing lifetime health risk.

Background

Empirical results of nonmarket valuation studies suggest that adults value improving their children's health more than their own. Such results are often explained by parental altruism, but self‐interest may also be involved.

Method

A choice experiment valuation survey elicited respondents' preferences for lifetime risk reduction in coronary artery disease (CAD) and a psychometric scale assessed their reciprocal attitudes. Respondents were middle‐generation members of three‐generation households. To conduct the analysis a hybrid mixed logit model was used that enabled including psychological factors into a utility function derived from respondents' survey choices.

Results

Reciprocal attitudes had distinct effects on the middle‐generation preferences for reducing family members' risk of CAD. The latent attitudes concerning reciprocity significantly affected the WTP for the health risk reduction for all family members. The impact of reciprocity on the valuation of CAD risk reduction for the respondent and the elderly parent was similar, but for the child, it was significantly higher.

Conclusions

Parents' higher WTP for improving children's health, at least partially, reflects strategic decisions related to reciprocal beliefs. Reciprocity also affects the evaluation of health benefits for elderly parents and middle‐aged respondents themselves.

Implications

These findings may have implications regarding the degree to which the so‐called “sandwich generation” can substitute for the government in the area of health and social care for the elderly.
REGULATORY PROTECTION AND THE ROLE OF INTERNATIONAL COOPERATION
Authors: Mei Yuan
Published: October 2023

I develop a general equilibrium framework to analyze the welfare consequences of product regulations and their international harmonization. In my model, raising product standards reduces a negative consumption externality, but also increases the marginal and fixed costs of production. When product standards are set noncooperatively, the effects of standards on other countries' wages and number of firms are not internalized, giving rise to an international inefficiency. The World Trade Organization's nondiscrimination principle of national treatment only partly addresses this inefficiency. Welfare losses from abandoning national treatment average 2.8%, whereas the maximum welfare gains from efficient cooperation average 11.8%.
Vaginal malignant peripheral nerve sheath tumor treated with complete surgical resection and postoperative radiation therapy
Authors: Mizuta Yuka , Kozono Yuki , Asai Mayu , Sekiyama Kentaro , Yoshioka Yumiko , Higuchi Toshihiro
Published: October 2023

Malignant peripheral nerve sheath tumors (MPNSTs) are neoplasms originating from or differentiating into nerve sheaths of peripheral nerves. Vaginal origin is rare, with only six vaginal primary cases reported to date. A 55‐year‐old woman presented to our hospital with a 7 cm vulvar mass. Tumor biopsy results were suspicious of sarcoma, and pelvic magnetic resonance imaging and hysterofiberscopy showed that the tumor originated from the lower vagina. The mass was transvaginally excised, and histological examination confirmed the diagnosis of a vaginal MPNST with negative surgical margins. The patient underwent radiotherapy because the risk of recurrence was high, owing to the large tumor size and high mitotic index. The patient remained recurrence‐free for 1 year after the primary treatment. This is the first case of a high‐risk vaginal MPNST that avoided early disease recurrence with additional radiotherapy after complete tumor resection.
Student Outcomes, Perspectives, and Experiences in Traditional and Flipped L2 American Sign Language Classrooms: A Partial Replication Study
Authors: Cripps Jody H. , Rosen Russell S. , Sever‐Hall Aimee M. , Cooper Sheryl B. , Fenicle Ronald
Published: October 2023

Foreign language classrooms have historically used classroom lecture‐based approaches for instruction. However, the flipped pedagogical approach was recently introduced into foreign language and other classrooms. Studies of the flipped classroom approach in spoken L2 classrooms have generally found a positive impact on student learning outcomes, perceptions and satisfaction compared with the traditional classroom approach. Cripps et al. (2021) found no difference in student learning outcomes and satisfaction between L2 American Sign Language traditional and flipped classrooms each taught by two different instructors. This study is a partial replication of Cripps et al. (2021) with both classes taught by the same instructor, using the traditional classroom data from the original study and comparing it to new data from the same instructor teaching in the flipped approach. Results show no major differences, suggesting that the flipped classroom approach is as viable as the traditional classroom approach regardless of the instructor.
Machine learning–assisted drift capacity prediction models for reinforced concrete columns with shape memory alloy bars
Authors: Lee Chang Seok , Mangalathu Sujith , Jeon Jong‐Su
Published: October 2023

Despite notable progress made in predicting the drift capacity of reinforced columns with steel bars, these techniques and methods are proven inapplicable for accurately predicting the drift capacity of RC columns reinforced with shape memory alloy (SMA) bars. This study employed machine learning (ML) to predict and design the drift limit state of concrete columns using SMA bars. To this end, a total of 292,000 synthetic data points were generated through numerical simulations given the limited amount of experimental data for SMA bars. The data analysis results suggest that the light gradient boosting (LGB) algorithm achieves the best performance in terms of computational efficiency and prediction accuracy among nine candidate ML algorithms considered in this study. Further refinements for the LGB algorithm is introduced to yield better prediction results: (1) Hyperparameters are tuned using particle swarm optimization with an improved particle updating strategy and (2) the dimensions of the input data are reduced using a modified recursive feature elimination algorithm with memorizing capability. In addition, this study demonstrated the application of the proposed ML‐assisted drift capacity prediction model to the design of SMA‐reinforced concrete columns using modified particle swarm optimization that can help structural designers worldwide.
Global analysis of seed transcriptomes reveals a novel PLATZ regulator for seed size and weight control in soybean
Authors: Hu Yang , Liu Yue , Lu Long , Tao Jian‐Jun , Cheng Tong , Jin Meng , Wang Zhou‐Ya , Wei Jun‐Jie , Jiang Zhi‐Hao , Sun Wan‐Cai , Liu Cheng‐Lan , Gao Feng , Zhang Yong , Li Wei , Bi Ying‐Dong , Lai Yong‐Cai , Zhou Bin , Yu De‐Yue , Yin Cui‐Cui , Wei Wei , Zhang Wan‐Ke , Chen Shou‐Yi , Zhang Jin‐Song
Published: October 2023

Seed size and weight are important factors that influence soybean yield.

Combining the weighted gene co‐expression network analysis (WGCNA) of 45 soybean accessions and gene dynamic changes in seeds at seven developmental stages, we identified candidate genes that may control the seed size/weight. Among these, a PLATZ‐type regulator overlapping with 10 seed weight QTLs was further investigated. This zinc‐finger transcriptional regulator, named as GmPLATZ, is required for the promotion of seed size and weight in soybean.

The GmPLATZ may exert its functions through direct binding to the promoters and activation of the expression of cyclin genes and GmGA20OX for cell proliferation. Overexpression of the GmGA20OX enhanced seed size/weight in soybean. We further found that the GmPLATZ binds to a 32‐bp sequence containing a core palindromic element AATGCGCATT. Spacing of the flanking sequences beyond the core element facilitated GmPLATZ binding. An elite haplotype Hap3 was also identified to have higher promoter activity and correlated with higher gene expression and higher seed weight. Orthologues of the GmPLATZ from rice and Arabidopsis play similar roles in seeds.

Our study reveals a novel module of GmPLATZ‐GmGA20OX/cyclins in regulating seed size and weight and provides valuable targets for breeding of crops with desirable agronomic traits.
Helper NLRs Nrc2 and Nrc3 act codependently with Prf/Pto and activate MAPK signaling to induce immunity in tomato
Authors: Zhang Ning , Gan Joyce , Carneal Lauren , González‐Tobón Juliana , Filiatrault Melanie , Martin Gregory B.
Published: October 2023

Plant intracellular immune receptors, primarily nucleotide‐binding, leucine‐rich repeat proteins (NLRs), detect pathogen effector proteins and activate NLR‐triggered immunity (NTI). Recently, ‘sensor’ NLRs have been reported to function with ‘helper’ NLRs to activate immunity. We investigated the role of two helper NLRs, Nrc2 and Nrc3, on immunity in tomato to the bacterial pathogen Pseudomonas syringae pv. tomato (Pst) mediated by the sensor NLR Prf and the Pto kinase. An nrc2/nrc3 mutant no longer activated Prf/Pto‐mediated NTI to Pst containing the effectors AvrPto and AvrPtoB. An nrc3 mutant showed intermediate susceptibility between wild‐type plants and a Prf mutant, while an nrc2 mutant developed only mild disease. These observations indicate that Nrc2 and Nrc3 act additively in Prf‐/Pto‐mediated immunity. We examined at what point Nrc2 and Nrc3 act in the Prf/Pto‐mediated immune response. In the nrc2/3 mutant, programmed cell death (PCD) normally induced by constitutively active variants of AvrPtoB, Pto, or Prf was abolished, but that induced by M3Kα or Mkk2 was not. PCD induced by a constitutively active Nrc3 was also abolished in a Nicotiana benthamiana line with reduced expression of Prf. MAPK activation triggered by expression of AvrPto in the wild‐type tomato plants was completely abolished in the nrc2/3 mutant. These results indicate that Nrc2 and Nrc3 act with Prf/Pto and upstream of MAPK signaling. Nrc2 and Nrc3 were not required for PCD triggered by Ptr1, another sensor NLR‐mediating Pst resistance, although these helper NLRs do appear to be involved in resistance to certain Pst race 1 strains