bluuebunny/crossref_metadata_2025 huggingface dataset:
Digital games as educational potential: Experiences and examples
Authors: Arsenijević Jasmina , Arsenijević Olja
Published: November 2022

Digital games also provide the opportunity to gain different experiences, broaden horizons, change behavior, and often socialize and network with other people. And while the initial stigmatization and suspicion of the scientific and professional, as well as the general public, is slowly decreasing, the trend and importance of the application of digital games in learning is growing, both at the level of individuals (through informal education) and institutions (through informal or formal). The number of researches on the effects of their application is increasing, especially since the beginning of the new millennium. This paper provides an overview of the educational potential of digital games and categorizes the results of the most significant research into the effects of their application in formal, non-formal and informal education. The paper illustrates the above results by going through numerous examples of specific mainstream or educational games.
Renewal of buses and registration of new buses in the Slovak Republic and the Czech Republic
Authors: Gnap Jozef , Dočkalik Marek
Published: November 2022

The use of alternative fuels and the use of vehicles meeting the strictest emission standards can contribute to improving the impact of road transport on the environment. Therefore, it is also very important to restore buses, which can affect the environment in cities to a certain extent. Achieving an increase in the number and share of ecological buses is possible through several tools. The contribution is focused on the analysis of the EU directive on the support of ecological and energy-saving road transport vehicles and the study of the number and share of ecological buses in European countries, and the data for the Slovak Republic and the Czech Republic, which can also be compared for the same period, are processed in more detail. Due to the growth rate of the number of ecological buses during the period under review, it can be seen that in the Slovak Republic it is definitely necessary to increase the number and the proportion of buses that have a more favourable impact on the environment and are considered ecological.
Modeling SMEs Credit Default Risk: The Case of Saudi Arabia
Authors: Tayachi Tahar , BenSaïda Ahmed
Published: November 2022

This study assesses the credit risk of small and medium-sized enterprises (SMEs) to minimize unexpected risk events. We construct a hybrid statistical model based on factor analysis and logistic regression to predict enterprise default on loans and determine the factors predicting SMEs default. We assess the credit risk of SMEs listed on the Saudi stock market. The results indicate that the SMEs acid-test ratios are the most influential factors in predicting SMEs credit risk. Therefore, the designed logistic model can be used by financial institutions during the decision-making process of granting loans to SMEs. This study sheds light on challenging access to bank credits due to the lack of financial transparency of most Saudi SMEs.
The Question of African Leadership: Nigeria in Focus
Authors: Nikez Adu Yao , Nwalie George Avele
Published: November 2022

This article is devoted to the study of the issue of leadership on the African continent, which is the object of the study, because, since 1963 Nigeria is a member of the Organization of African Unity (now the African Union), the Economic Community of West African States since 1975, and the United Nations since October 7, 1960. The subject of the study is Nigeria’s foreign policy on the African continent, as since independence Nigeria has pursued a number of foreign policy goals: the eradication of colonialism and other external forms of exploitation, The oppression and marginalization of Africans. The main conclusion of the study is that Nigeria’s role in the formation of AU and ECOWAS, was in conformity with its national interest and foreign policy pursuit, which was designed to promote regional integration and cooperation within West Africa and Africa in general. The role of Nigeria is fundamental for African organizations and their leadership prospects. Historically, Nigeria's Afrocentric foreign policy and its national interest have made it possible for Nigeria to pursue African oriented policy. The authors applied a number of methods to carry out this research: historical, legal and analytical. The historical method allows us to give the chronology of Nigeria’s leadership role in Africa from 1960 to 2020. The legal method permitted the analysis of the legal instruments, particularly from different constitutions, treaties since Nigeria’s independence till date. The analytical method consists of the analysis of the evolution of different transformations that occurred in the African continent from 1960 to 2020.
Development and Use of the Expert Assessment Method for Ranking Threats to the National Security of the Russian Federation
Authors: Starovoitov Vladimir Gavrilovich , Krupnov Yurii Aleksandrovich , Eremin Vladimir Vladimirovich , Zolotarev Evgenii Vladimirovich , Lapenkova Natalya Vladimirovna
Published: November 2022

The subject of the research is the method of expert assessments for ranking threats to the national security of the Russian Federation. The object of research is the process of ensuring the national security of the Russian Federation. The following expert methods are considered in the article: direct placement method; method of analysis of hierarchies; method of expert ranking of factors influencing the result. In this study, the existing approaches to the activities of expert groups based on the method of ranking factors are considered in more detail. Within the framework of this method, factors are ordered according to the degree of manifestation of their properties and influence on the ultimate goal (national security) in ascending or descending order. The method is used when it is impossible to quantify the factors that determine the course of processes in socio-economic systems. The scientific novelty of the use of expert approaches is substantiated by the authors by the lack of necessary statistical information on the quantitative characteristics of the relationship between threats to the national security of the Russian Federation and the factors that form them, as well as by the possibility of filling this gap by expert means. The article presents the results of a survey of 23 experts - specialists in the field of national and economic security on the ranking of threats identified in the National Security Strategy of the Russian Federation. The authors conclude that the use of the method of expert assessments for ranking threats on a point scale makes it possible to determine the most significant and urgent threats to national security based on the experience and knowledge of highly professional experts. The method is simple, understandable and convenient for decision makers, and gives them the opportunity to quickly take measures to minimize and neutralize threats to national security in order to further strengthen it. The technology of forming an expert group and conducting an online survey of experts can be widely used in Russian practice in solving problems to ensure the national security of the country.
"Chinese Style" in the Piano Piece "Spring Dance"
Authors: Du Wenting
Published: November 2022

Although the piano is an instrument with more than three hundred years of history, it has not been in China for a long time. Therefore, in the process of learning to play the piano in China, many Western piano works are often played, but rarely come into contact with Chinese-style piano works. With the development of time, thanks to the relentless search for outstanding Chinese composers, more and more piano works based on ethnic culture and Chinese style appear. Some of these works are based on the music of national minorities, some are adaptations of Chinese folk songs, and some are borrowed from folk music. "Spring Dance" is a typical work reflecting the culture of the Uighurs living in Xinjiang. The work is melodic, rhythmic, expresses the beautiful nature of Xinjiang, the warm and energetic character of the Uighur people.This article analyzes the "Chinese style" of the "Spring Dance" in the hope that it will serve as a basis for studying piano works with Chinese national flavor. The "Chinese style" in rhythms is not only an imitation of the rhythms of traditional folk instruments, but also an imitation of the peculiarities of the language of Chinese national minorities. Thanks to the study of the "Chinese style" in this work, the author understood more deeply the unique charm of Chinese piano works which will also serve as a guide for the subsequent study of such piano works.
Evolution and regulation of microbial secondary metabolism
Authors: Santamaria Guillem , Liao Chen , Lindberg Chloe , Chen Yanyan , Wang Zhe , Rhee Kyu , Pinto Francisco Rodrigues , Yan Jinyuan , Xavier Joao B
Published: November 2022

Microbes have disproportionate impacts on the macroscopic world. This is in part due to their ability to grow to large populations that collectively secrete massive amounts of secondary metabolites and alter their environment. Yet, the conditions favoring secondary metabolism despite the potential costs for primary metabolism remain unclear. Here we investigated the biosurfactants that the bacterium Pseudomonas aeruginosa makes and secretes to decrease the surface tension of surrounding liquid. Using a combination of genomics, metabolomics, transcriptomics, and mathematical modeling we show that the ability to make surfactants from glycerol varies inconsistently across the phylogenetic tree; instead, lineages that lost this ability are also worse at reducing the oxidative stress of primary metabolism on glycerol. Experiments with different carbon sources support a link with oxidative stress that explains the inconsistent distribution across the P. aeruginosa phylogeny and suggests a general principle: P. aeruginosa lineages produce surfactants if they can reduce the oxidative stress produced by primary metabolism and have excess resources, beyond their primary needs, to afford secondary metabolism. These results add a new layer to the regulation of a secondary metabolite unessential for primary metabolism but important to change physical properties of the environments surrounding bacterial populations.
Measurements of damage and repair of binary health attributes in aging mice and humans reveal that robustness and resilience decrease with age, operate over broad timescales, and are affected differently by interventions
Authors: Farrell Spencer , Kane Alice E , Bisset Elise , Howlett Susan E , Rutenberg Andrew D
Published: November 2022

As an organism ages, its health-state is determined by a balance between the processes of damage and repair. Measuring these processes requires longitudinal data. We extract damage and repair transition rates from repeated observations of binary health attributes in mice and humans to explore robustness and resilience, which respectively represent resisting or recovering from damage. We assess differences in robustness and resilience using changes in damage rates and repair rates of binary health attributes. We find a conserved decline with age in robustness and resilience in mice and humans, implying that both contribute to worsening aging health – as assessed by the frailty index (FI). A decline in robustness, however, has a greater effect than a decline in resilience on the accelerated increase of the FI with age, and a greater association with reduced survival. We also find that deficits are damaged and repaired over a wide range of timescales ranging from the shortest measurement scales toward organismal lifetime timescales. We explore the effect of systemic interventions that have been shown to improve health, including the angiotensin-converting enzyme inhibitor enalapril and voluntary exercise for mice. We have also explored the correlations with household wealth for humans. We find that these interventions and factors affect both damage and repair rates, and hence robustness and resilience, in age and sex-dependent manners.
Collateral deletion of the mitochondrial AAA+ ATPase ATAD1 sensitizes cancer cells to proteasome dysfunction
Authors: Winter Jacob M , Fresenius Heidi L , Cunningham Corey N , Wei Peng , Keys Heather R , Berg Jordan , Bott Alex , Yadav Tarun , Ryan Jeremy , Sirohi Deepika , Tripp Sheryl R , Barta Paige , Agarwal Neeraj , Letai Anthony , Sabatini David M , Wohlever Matthew L , Rutter Jared
Published: November 2022

The tumor suppressor gene PTEN is the second most commonly deleted gene in cancer. Such deletions often include portions of the chromosome 10q23 locus beyond the bounds of PTEN itself, which frequently disrupts adjacent genes. Coincidental loss of PTEN-adjacent genes might impose vulnerabilities that could either affect patient outcome basally or be exploited therapeutically. Here, we describe how the loss of ATAD1, which is adjacent to and frequently co-deleted with PTEN, predisposes cancer cells to apoptosis triggered by proteasome dysfunction and correlates with improved survival in cancer patients. ATAD1 directly and specifically extracts the pro-apoptotic protein BIM from mitochondria to inactivate it. Cultured cells and mouse xenografts lacking ATAD1 are hypersensitive to clinically used proteasome inhibitors, which activate BIM and trigger apoptosis. This work furthers our understanding of mitochondrial protein homeostasis and could lead to new therapeutic options for the hundreds of thousands of cancer patients who have tumors with chromosome 10q23 deletion.
Comparative genome-wide methylation analysis reveals epigenetic regulation of muscle development in grass carp (Ctenopharyngodon idellus) fed with whole faba bean
Authors: Li Yichao , Fu Bing , Zhang Junming , Wang Guangjun , Tian Jingjing , Li Hongyan , Xia Yun , Xie Jun , Yu Ermeng
Published: November 2022

Crisp grass carp (CGC), the most representative improved varieties of grass carp (GC), features higher muscle hardness after feeding faba bean (Vicia faba L.) for 90–120 days. DNA methylation, a most widely studied epigenetic modification, plays an essential role in muscle development. Previous studies have identified numerous differentially expressed genes (DEGs) between CGC and GC. However, it remains unknown if the expression levels of these DEGs are influenced by DNA methylation. In the present study, we performed a comprehensive analysis of DNA methylation profiles between CGC and GC, and identified important candidate genes related to muscle development coupled with the transcriptome sequencing data. A total of 9,318 differentially methylated genes (DMGs) corresponding to 155,760 differentially methylated regions (DMRs) were identified between the two groups under the CG context in promoter regions. Combined with the transcriptome sequencing data, 14 key genes related to muscle development were identified, eight of which (gsk3b, wnt8a, wnt11, axin2, stat1, stat2, jak2, hsp90) were involved in muscle fiber hyperplasia, six of which (tgf-β1, col1a1, col1a2, col1a3, col4a1, col18a1) were associated with collagen synthesis in crisp grass carp. The difference of methylation levels in the key genes might lead to the expression difference, further resulting in the increase of muscle hardness in crisp grass carp. Overall, this study can help further understand how faba bean modulates muscle development by the epigenetic modifications, providing novel insights into the texture quality improvement in other aquaculture fish species by nutritional programming.
Chemical composition, antioxidant and anti-inflammatory properties of Monarda didyma L. essential oil
Authors: Fraternale Daniele , Dufat Hanh , Albertini Maria Cristina , Bouzidi Chouaha , D’Adderio Rossella , Coppari Sofia , Di Giacomo Barbara , Melandri Davide , Ramakrishna Seeram , Colomba Mariastella
Published: November 2022

In the present study, Monarda didyma L. essential oil (isolated from the flowering aerial parts of the plant) was examined to characterize its chemotype and to evaluate, in addition to the quali-quantitative chemical analysis, the associated antioxidant and anti-inflammatory activities. The plants were grown in central Italy, Urbino (PU), Marche region. Different analyses (TLC, GC-FID, GC-MS and 1H-NMR) allowed the identification of twenty compounds among which carvacrol, p-cymene and thymol were the most abundant. On this basis, the chemotype examined in the present study was indicated as Monarda didyma ct. carvacrol. The antioxidant effect was assessed by DPPH assay. Moreover, this chemotype was investigated for the anti-inflammatory effect in an in vitro setting (i.e., LPS-stimulated U937 cells). The decreased expression of pro-inflammatory cytokine IL-6 and the increased expression of miR-146a are suggestive of the involvement of the Toll-like receptor-4 signaling pathway. Although further studies are needed to better investigate the action mechanism/s underlying the results observed in the experimental setting, our findings show that M. didyma essential oil is rich in bioactive compounds (mainly aromatic monoterpenes and phenolic monoterpenes) which are most likely responsible for its beneficial effect.
Ear your heart: transcutaneous auricular vagus nerve stimulation on heart rate variability in healthy young participants
Authors: Forte Giuseppe , Favieri Francesca , Leemhuis Erik , De Martino Maria Luisa , Giannini Anna Maria , De Gennaro Luigi , Casagrande Maria , Pazzaglia Mariella
Published: November 2022

Background

Transcutaneous auricular vagus nerve stimulation (taVNS) stimulating the auricular branch of the vagus nerve along a well-defined neuroanatomical pathway, has promising therapeutic efficacy. Potentially, taVNS can modulate autonomic responses. Specifically, taVNS can induce more consistent parasympathetic activation and may lead to increased heart rate variability (HRV). However, the effects of taVNS on HRV remain inconclusive. Here, we investigated changes in HRV due to brief alteration periods of parasympathetic-vagal cardiac activity produced by taVNS on the cymba as opposed to control administration via the helix.

Materials and Methods

We compared the effect of 10 min of active stimulation (i.e., cymba conchae) to sham stimulation (i.e., helix) on peripheral cardiovascular response, in 28 healthy young adults. HRV was estimated in the time domain and frequency domain during the overall stimulation.

Results

Although active-taVNS and sham-taVNS stimulation did not differ in subjective intensity ratings, the active stimulation of the cymba led to vagally mediated HRV increases in both the time and frequency domains. Differences were significant between active-taVNS and both sham-taVNS and resting conditions in the absence of stimulation for various HRV parameters, but not for the low-frequency index of HRV, where no differences were found between active-taVNS and sham-taVNS conditions.

Conclusion

This work supports the hypothesis that taVNS reliably induces a rapid increase in HRV parameters when auricular stimulation is used to recruit fibers in the cymba compared to stimulation at another site. The results suggest that HRV can be used as a physiological indicator of autonomic tone in taVNS for research and potential therapeutic applications, in line with the established effects of invasive VNS. Knowledge of the physiological effect of taVNS short sessions in modulating cardiovagal processing is essential for enhancing its clinical use.
Increased vitamin D intake may reduce psychological anxiety and the incidence of menstrual irregularities in female athletes
Authors: Miyamoto Mana , Hanatani Yuko , Shibuya Kenichi
Published: November 2022

Background

Vitamin D deficiency has been associated with major depression and premenstrual mood symptoms, and menstrual irregularity has been correlated with mental anxiety. However, the potential effect of increased vitamin D intake on reducing the risk of menstrual irregularities by decreasing psychological anxiety is yet to be fully elucidated. The existence of such a relationship in athletes with high levels of psychological anxiety and adequate dietary intake remains unknown. Therefore, this study aimed to examine the effects of vitamin D intake on psychological anxiety levels and the risk of menstrual irregularities in healthy college-and international-level female athletes.

Methods

Female intercollege-level track and field and international-level rowing athletes (n= 107) aged 15–24 years were included in this study. Their nutritional intake, body mass, body fat, mental anxiety, and menstrual irregularities were investigated. A generalized linear mixed model (GLMM) was used to examine the effects of several parameters on menstrual irregularities. The independent variables introduced into the GLMM were determined based on Akaike’s information criterion.

Results

The GLMM identified a significant interaction effect of vitamin D intake and state anxiety on menstrual irregularities, with ap-value of 0.049 and an odds ratio of 0.423. The study results suggest that increased vitamin D intake in relatively young endurance athletes may reduce mental anxiety, consequently decreasing menstrual irregularities.
Ophthalmology in Ancient Egypt
Authors: Güemes Luciana Acosta , Cusumano Ana María
Published: November 2022

The civilization of Ancient Egypt is the one that has the most references regarding the work of ophthalmologists, compared to the rest of the ancient civilizations. There are complete anatomical and treatment descriptions. Pepi Ankh Or Iri, who lived between 2270 and 2210 BC, is recognized as the first documented ophthalmologist in history. Ophthalmological cures were carried out with prayers, incantations, astrology for prognosis, amulets and pharmacotherapy with eye drops and ointments. Details of ophthalmologic surgery are unknown. The Edwin Smith (1600 BC), Ebers (1550 BC), Hearst (1550 BC) and London (1300 BC) medical papyri include ophthalmological pathologies. Ophthalmological medical assistance was in charge of lay doctors or swnw, priests and magicians, who worked together, since they believed that the origin of diseases was the result of external agents, as well as supernatural causes. The importance of this historical review article lies in pointing out some of the avant-garde aspects of the ancient Egyptian civilization with respect to ophthalmology and its practice, and the coexistence in their society of a rational medical practice together with a magical-religious approach.
The Role of Trade Openness and its Implications for the Growth of the Iraqi Economy After 2003
Authors: Ibrahim Noor Abdul-Sattar
Published: November 2022

Due to its significant impact on economic growth in the context of the natural economy, the research aims to shed light on the extentof the Iraqi economy's commercial openness to the outside world and the impact of that openness on some of the economic variables, as it positively affects raising the rate of economic growth as a result of competition between imported goods and the economy's actual need for those goods. To do this, a few trade openness metrics for Iraq were collected and examined. The findings indicated a good correlation between GDP and trade openness. Additionally, an extensive amount of economic exposure to foreign markets is evident from the examination of the indicator of the level of economic exposure in the Iraqi economy. Additionally, this would hurt the state of the economy, economic activity, and development
Risk factors for pressure injury in patients with covid-19 in intensive care unit / Fatores de Risco para Lesão Por Pressão em Pacientes com COVID-19 em Unidade de Terapia Intensiva
Authors: Povoas Costa Letícia , Silva Barcellos Caetano Danielle , Silva dos Santos Juliana , Silva Solano Ramos dos Santos Paloma
Published: November 2022

Objetivo: identificar e discutir os fatores de risco relacionados à ocorrência de lesão por pressão em pacientes com COVID-19 em Unidade de Terapia Intensiva. Método: estudo descritivo de abordagem quantitativa e retrospectiva que analisou prontuários eletrônicos de um Hospital Militar, no período de abril a dezembro de 2020. Resultados: participaram do estudo 44 (55%) pacientes com idade média de 68,73 anos e predominância do gênero masculino (35%). A região sacra (32%) foi a mais acometida, seguida concomitantemente das regiões sacra e calcâneo (20%) e o estágio 2 (31,8%) se mostrou mais frequente. Observou-se como fatores de risco o tempo de internação, o uso de ventilação mecânica, a pronação, o uso drogas vasoativas e sedativos contínuos, a antibioticoterapia, a permanência de dieta enteral e/ou dieta zero. Conclusão: a implementação de estratégias para prevenção de lesão por pressão é de extrema importância, pois é uma das metas internacionais de segurança do paciente.
Cervical Cancer Incidence Among US Women, 2001-2019
Authors: Shahmoradi Zahed , Damgacioglu Haluk , Clarke Megan A. , Wentzensen Nicolas , Montealegre Jane , Sonawane Kalyani , Deshmukh Ashish A.
Published: November 2022

This study uses national cancer incidence data to evaluate calendar trends in cervical cancer incidence by age at diagnosis.
Medicare 2.0—A Vision for the Future of America’s Health Insurance Plan
Authors: Johnson Micah , Berwick Donald M.
Published: November 2022

This Viewpoint offers recommendations to unify various Medicare reform proposals to optimize the health insurance plan.
Trends in the Concurrent Prescription of Opioids and Gabapentin in the US, 2006 to 2018
Authors: Peet Evan D. , Dana Beth , Sheng Flora Yaou , Powell David , Shetty Kanaka , Stein Bradley D.
Published: November 2022

This cohort study examines trends in concurrent gabapentin and opioid prescribing in the US, overall and by prescriber, patient, and county characteristics, between 2006 and 2018.
Gender Differences in Emergency Medicine Attending Physician Comments to Residents: A Qualitative Analysis
Authors: Mamtani Mira , Shofer Frances , Scott Kevin , Kaminstein Dana , Eriksen Whitney , Takacs Michael , Hall Andrew K. , Weiss Anna , Walter Lauren A. , Gallahue Fiona , Yarris Lainie , Abbuhl Stephanie B. , Aysola Jaya
Published: November 2022

Importance

Prior studies have revealed gender differences in the milestone and clinical competency committee assessment of emergency medicine (EM) residents.

Objective

To explore gender disparities and the reasons for such disparities in the narrative comments from EM attending physicians to EM residents.

Design, Setting, and Participants

This multicenter qualitative analysis examined 10 488 narrative comments among EM faculty and EM residents between 2015 to 2018 in 5 EM training programs in the US. Data were analyzed from 2019 to 2021.

Main Outcomes and Measures

Differences in narrative comments by gender and study site. Qualitative analysis included deidentification and iterative coding of the data set using an axial coding approach, with double coding of 20% of the comments at random to assess intercoder reliability (κ, 0.84). The authors reviewed the unmasked coded data set to identify emerging themes. Summary statistics were calculated for the number of narrative comments and their coded themes by gender and study site. χ2 tests were used to determine differences in the proportion of narrative comments by gender of faculty and resident.

Results

In this study of 283 EM residents, of whom 113 (40%) identified as women, and 277 EM attending physicians, of whom 95 (34%) identified as women, there were notable gender differences in the content of the narrative comments from faculty to residents. Men faculty, compared with women faculty, were more likely to provide either nonspecific comments (115 of 182 [63.2%] vs 40 of 95 [42.1%]), or no comments (3387 of 10 496 [32.3%] vs 1169 of 4548 [25.7%]; P < .001) to men and women residents. Compared with men residents, more women residents were told that they were performing below level by men and women faculty (36 of 113 [31.9%] vs 43 of 170 [25.3%]), with the most common theme including lack of confidence with procedural skills.

Conclusions and Relevance

In this qualitative study of narrative comments provided by EM attending physicians to residents, multiple modifiable contributors to gender disparities in assessment were identified, including the presence, content, and specificity of comments. Among women residents, procedural competency was associated with being conflated with procedural confidence. These findings can inform interventions to improve parity in assessment across graduate medical education.
Association of Youth Suicides and County-Level Mental Health Professional Shortage Areas in the US
Authors: Hoffmann Jennifer A. , Attridge Megan M. , Carroll Michael S. , Simon Norma-Jean E. , Beck Andrew F. , Alpern Elizabeth R.
Published: November 2022

Importance

Suicide is the second leading cause of death among US adolescents. Workforce shortages of mental health professionals in the US are widespread, but the association between mental health workforce shortages and youth suicides is not well understood.

Objective

To assess the association between youth suicide rates and mental health professional workforce shortages at the county level, adjusting for county demographic and socioeconomic characteristics.

Design, Setting, and Participants

This retrospective cross-sectional study included all US counties and used data of all US youlth suicides from January 2015, through December 31, 2016. Data were analyzed from July 1, 2021, through December 20, 2021.

Exposures

County health-professional shortage area designation for mental health, assigned by the US Health Resources and Services Administration based on mental health professionals relative to the population, level of need for mental health services, and service availability in contiguous areas. Designated shortage areas receive a score from 0 to 25, with higher scores indicating greater workforce shortages.

Main Outcomes and Measures

Suicides by youth aged 5 to 19 years from 2015 to 2016 were identified from the US Centers for Disease Control and Prevention’s Compressed Mortality File. A multivariable negative binomial regression model was used to analyze the association between youth suicide rates and mental health workforce shortage designation, adjusting for the presence of a children’s mental health hospital and county-level markers of health insurance coverage, education, unemployment, income, poverty, urbanicity, racial and ethnic composition, and year. Similar models were performed for the subgroups of (1) firearm suicides and (2) counties assigned a numeric shortage score.

Results

During the study period, there were 5034 youth suicides (72.8% male and 68.2% non-Hispanic White) with an annual suicide rate of 3.99 per 100 000 youths. Of 3133 US counties, 2117 (67.6%) were designated as mental health workforce shortage areas. After adjusting for county characteristics, mental health workforce shortage designation was associated with an increased youth suicide rate (adjusted incidence rate ratio [aIRR], 1.16; 95% CI, 1.07-1.26) and an increased youth firearm suicide rate (aIRR, 1.27; 95% CI, 1.13-1.42). For counties with an assigned numeric workforce shortage score, the adjusted youth suicide rate increased 4% for every 1-point increase in the score (aIRR, 1.04; 95% CI, 1.02-1.06).

Conclusions and Relevance

In this cross-sectional study, US county mental health professional workforce shortages were associated with increased youth suicide rates. These findings may inform suicide prevention efforts.
Effect of a Virtual Reality Environment Using a Domed Ceiling Screen on Procedural Pain During Intravenous Placement in Young Children
Authors: Lee Ha Ni , Park Joong Wan , Hwang Soyun , Jung Jae Yun , Kim Do Kyun , Kwak Young Ho , Lee Eui Jun
Published: November 2022

Importance

Distraction using virtual reality (VR) has been found to provide a clinically significant reduction in the experience of pain during various painful procedures. Commercially available VR systems usually require the user to wear a head-mounted display helmet, which can be challenging for young children, and whether VR can reduce pain during intravenous (IV) placement in young children is currently unknown.

Objective

To determine whether a VR environment using a novel domed ceiling screen reduces distress among children over the course of IV placement compared with standard care in a pediatric emergency department.

Design, Setting, and Participants

This randomized clinical trial was conducted from June 3, 2020, to February 8, 2021, at an urban tertiary academic children’s hospital. Included were children aged 6 months to 4 years undergoing IV placement in the pediatric emergency department.

Intervention

Children in the intervention group lay on a bed to experience a VR animation using a domed ceiling screen during the IV placement procedure, which was performed as usual. Children in the control group also lay on a bed during the procedure but did not view a VR animation.

Main Outcomes and Measures

The primary outcome was pain scores measured using the Face, Legs, Activity, Cry, and Consolability (FLACC) scale at 4 time points during IV placement: immediately after the child lay down on the bed (T1), the moment the tourniquet was applied (T2), the moment a sterile alcohol swab was applied (T3), and the moment the needle penetrated the skin (T4).

Results

Of the 88 children included in the final analysis, 44 received VR distraction (median [IQR] age, 24.0 [14.5-44.0] months; 27 boys [61.4%]), and 44 received standard care (median [IQR] age, 23.0 [15.0-40.0] months; 26 boys [59.1%]). The median [IQR] FLACC scores at T4 were 6.0 (1.8-7.5) in the intervention group and 7.0 (5.5-7.8) in the control group. The ordinal logistic regression model showed that children in the VR intervention group vs the control group had a lower probability of higher FLACC scores (odds ratio, 0.53; 95% CI, 0.28-0.99; P = .046).

Conclusions and Relevance

The findings of this trial indicate that displaying VR using a domed ceiling screen may be an effective distraction method that reduces distress in young children undergoing IV placement.

Trial Registration

isrctn.org Identifier: KCT0005122
Oxidative stress‐induced FAK activation contributes to uterine serous carcinoma aggressiveness
Authors: Lopez‐Mejia Isabel C. , Pijuan Jordi , Navaridas Raúl , Santacana Maria , Gatius Sònia , Velasco Ana , Castellà Gerard , Panosa Anaïs , Cabiscol Elisa , Pinyol Miquel , Coll Laura , Bonifaci Núria , Peña Laura Plata , Vidal August , Villanueva Alberto , Gari Eloi , Llobet‐Navàs David , Fajas Lluis , Matias‐Guiu Xavier , Yeramian Andrée
Published: November 2022

Uterine serous carcinoma (USC) is an aggressive form of endometrial cancer (EC), characterized by its high propensity for metastases. In fact, while endometrioid endometrial carcinoma (EEC), which accounts for 85% of EC, presents a good prognosis, USC is the most frequently fatal. Herein, we used for the first time a peptide‐based tyrosine‐kinase‐activity profiling approach to quantify the changes in tyrosine kinase activation between USC and EEC. Among the tyrosine kinases highly activated in USC, we identified focal adhesion kinase (FAK). We conducted mechanistic studies using cellular models. In a USC cell line, targeting FAK either by inhibitors PF‐573228 and defactinib (VS‐6063) or by gene silencing limits 3D cell growth and reduces cell migration. Moreover, results from our studies suggest that oxidative stress is increased in USC tumors compared to EEC ones. Reactive oxygen species (ROS) induce tyrosine phosphorylation of FAK and a concomitant tyrosine phosphorylation of paxillin, a mediator of FAK signal transduction. Mechanistically, by tracking hundreds of individual cells per condition, we show that ROS increased cell distance and migration velocity, highlighting the role of ROS‐FAK‐PAX signaling in cell migration. Both defactinib and ROS scavenger N‐acetylcysteine (NAC) revert this effect, pointing toward ROS as potential culprits for the increase in USC cell motility. A proof of concept of the role of FAK in controlling cell growth was obtained in in vivo experiments using cancer‐tissue‐originated spheroids (CTOS) and a patient‐derived orthotopic xenograft model (orthoxenograft/PDOX). Defactinib reduces cell proliferation and protein oxidation, supporting a pro‐tumoral antioxidant role of FAK, whereas antioxidant NAC reverts FAK inhibitor effects. Overall, our data points to ROS‐mediated FAK activation in USC as being responsible for the poor prognosis of this tumor type and emphasize the potential of FAK inhibition for USC treatment.
GALNT2 promotes invasiveness of colorectal cancer cells partly through AXL
Authors: Liao Ying‐Yu , Chuang Ya‐Ting , Lin Hsuan‐Yu , Lin Neng‐Yu , Hsu Tzu‐Wen , Hsieh Szu‐Chia , Chen Syue‐Ting , Hung Ji‐Shiang , Yang Hung‐Jen , Liang Jin‐Tung , Huang Min‐Chuan , Huang John
Published: November 2022

GalNAc‐type O‐glycosylation and its initiating GalNAc transferases (GALNTs) play crucial roles in a wide range of cellular behaviors. Among 20 GALNT members, GALNT2 is consistently associated with poor survival of patients with colorectal cancer in public databases. However, its clinicopathological significance in colorectal cancer remains unclear. In this study, immunohistochemistry showed that GALNT2 was overexpressed in colorectal tumors compared with the adjacent nontumor tissues. GALNT2 overexpression was associated with poor survival of colorectal cancer patients. Forced expression of GALNT2 promoted migration and invasion as well as peritoneal metastasis of colorectal cancer cells. In contrast, GALNT2 knockdown with siRNAs or knockout with CRISPR/Cas9 system suppressed these malignant properties. Interestingly, we found that GALNT2 modified O‐glycans on AXL and determined AXL levels via the proteasome‐dependent pathway. In addition, the GALNT2‐promoted invasiveness was significantly reversed by AXL siRNAs. These findings suggest that GALNT2 promotes colorectal cancer invasion at least partly through AXL.
Development and Validation of an Emergency Department Electronic Medical Record Gout Flare Alert
Authors: Jackson Lesley E. , Annapureddy Narender , Hansen Megan E. , Saag Kenneth G. , Booth James , Rosas Giovanna , Foster Phillip J. , Mudano Amy , Sun Dongmei , Osborne John D. , Bongartz Tim , Hess Erik , Lawrence Colleen , Dunkel Leah , Danila Maria I.
Published: November 2022

Objective

Patients with acute gout are frequently treated in the emergency department (ED) and represent a typically underresourced and understudied population. A key limitation for gout research in the ED is the timely ability to identify acute gout patients. Our goal was to refine a multicriteria, electronic medical record alert for gout flares and to determine its diagnostic characteristics in the ED.

Methods

The gout flare alert used electronic medical record data from ED nursing notes and was triggered by the term ‘gout’ preceding past medical history in the chief complaint, the term ‘gout’ and a musculoskeletal problem in the chief complaint, or the term ‘gout’ in the problem list and a musculoskeletal chief complaint. We validated its diagnostic properties to assess presence/absence of gout through manual medical record review using adjudicated expert consensus as the gold standard.

Results

In January 2020, we analyzed 202 patient records from 2 university‐based EDs; from these records, 57 patients were identified by our gout flare alert, and 145 were identified by other means as potentially having an acute gout flare. The gout flare alert's positive predictive value was 47% (95% confidence interval [95% CI] 34–60%), negative predictive value was 94% (95% CI 90–98%), sensitivity was 75% (95% CI 61–89%), and specificity was 82% (95% CI 76–88%). The diagnostic properties were similar at both institutions.

Conclusion

Our multicomponent gout flare alert had reasonable sensitivity and specificity, albeit a modest positive predictive value. An electronic gout flare alert may help enable the conduct of gout research in the ED setting.
Structural Stability Boosted in 3D Carbon‐Free Iron Selenide through Engineering Heterointerfaces with SeP Bonds for Appealing Na+‐Storage
Authors: Xiao Ying , Miao Yue , Hu Shilin , Gong Fenglian , Yu Qingtao , Zhou Luoyuan , Chen Shimou
Published: November 2022

Iron selenides have emerged as appealing anodes for Na+‐storage due to their natural abundance, good redox reversibility, and high theoretical capacity. Nevertheless, exploring a carbon‐free iron selenide anode with long‐term stability and high‐rate capability remains an intractable challenge. Herein, a 3D carbon‐free iron selenide electrode is designed by heterointerface with SeP bond engineering strategy to realize outstanding Na+‐storage performance. Theoretical calculations on the stress deformation confirm the construction of Fe7Se8/Fe3(PO4)2 not only enables excellent resistance‐to‐deformation ability but also exhibits strong mechanically stable against sodiation–desodiation. Such fascinating properties combined with the accelerated Na+ diffusion kinetics and enhanced electronic conductivity endowed by the 3D interconnected framework contribute to impressive cycling stability and superb rate performance for Na+‐storage. Consequently, the designed 3D Fe7Se8/Fe3(PO4)2 composite with a high tap density of 0.91 cm3 g−1 displays a stable specific capacity of 277.1 mAh cm−3 at 30 A g−1, and outstanding long‐term cycle stability of up to 1500 cycles at 5 A g−1 without obvious capacity decay. The proposed engineering strategy and results provide new insight to design carbon‐free advanced electrodes for future practical applications.
Boosting ROS‐Mediated Lysosomal Membrane Permeabilization for Cancer Ferroptosis Therapy
Authors: Chen Ying , Yang Zengqiu , Wang Sibu , Ma Qin , Li Lingyan , Wu Xingjie , Guo Qianqian , Tao Ling , Shen Xiangchun
Published: November 2022

Due to the deficient catalase, abundant reduced iron and low acidic environment in lysosomes, inducing lysosomal membrane permeabilization (LMP) through Fenton reaction‐based reactive oxygen species (ROS) generation recently attracts increasing attention in cancer therapy. However, the lysosomal membranes are protected by highly glycosylated membrane proteins and several endolysosomal damage‐response mechanisms can rapidly repair the injured lysosomes. To produce sufficient ROS and cause complete lysosomal membranes rupture, a lysosome‐targeted ROS inducer, N‐(3‐Aminopropyl) morpholine grafted cross‐linked lipoic acid vesicles with vitamin C‐loading (VC@N3AMcLAVs), is developed. VC@N3AMcLAVs efficiently accumulate in lysosomes and convert into two redox couples LA/DHLA (dihydrolipoic acid, reduced form of LA) and VC/DHA (dehydroascorbic acid, oxidized form of VC) by the lysosomal glutathione, which can not only produce a large amount of H2O2 by pro‐oxidant action but also accelerate iron transformation through the cyclic redox reactions between each other and cause the efficient conversion of the generated H2O2 into highly toxic •OH. Both in vitro and in vivo experiments demonstrate that VC@N3AMcLAVs can effectively enhance ROS production and boost LMP, finally initiation irreversible death of tumor cells via ferroptosis pathway, thus representing a potential anticancer drug for cancer therapy.
Surface Engineering of Auxetic Scaffolds for Neural and Vascular Differentiation from Human Pluripotent Stem Cells
Authors: Chen Xingchi , Liu Chang , Wadsworth Matthew , Zeng Eric Z. , Driscoll Tristan , Zeng Changchun , Li Yan
Published: November 2022

Auxetic materials are the materials that can display negative Poisson's ratio that describes the degree to which a material contracts (or expands) transversally when axially strained. Human stem cells sense the mechanical properties of the microenvironment, including material surface properties, stiffness, and Poisson's ratio. In this study, six different auxetic polyurethane (PU) foams with different elastic modulus (0.7–1.8 kPa) and Poisson's ratio (−0.1 to −0.5) are used to investigate lineage specification of human induced pluripotent stem cells (hiPSCs). The surfaces of the foams are modified with chitosan or heparin to enhance the adhesion and proliferation of hiPSCs. Then, the vascular and neural differentiation of hiPSCs are investigated on different foams with distinct elastic modulus and Poisson's ratio. With different auxetic foams, cells show differential adherent density and differentiation capacity. Chitosan and heparin surface functionalization promote the hindbrain and hippocampal markers, but not forebrain markers during neural patterning of hiPSCs. Properly surface engineered auxetic scaffolds can also promote vascular differentiation of hiPSCs. This study represents a versatile and multifunctional scaffold fabrication approach and can lead to a suitable system for establishing hiPSC culture models in applications of neurovascular disease modeling and drug screening.
Stable Zn Anodes with Triple Gradients
Authors: Gao Yong , Cao Qinghe , Pu Jie , Zhao Xin , Fu Gangwen , Chen Jipeng , Wang Yuxuan , Guan Cao
Published: November 2022

Aqueous zinc‐ion batteries are highly desirable for sustainable energy storage, but the undesired Zn dendrites growth severely shortens the cycle life. Herein, a triple‐gradient electrode that simultaneously integrates gradient conductivity, zincophilicity, and porosity is facilely constructed for a dendrite‐free Zn anode. The simple mechanical rolling‐induced triple‐gradient design effectively optimizes the electric field distribution, Zn2+ ion flux, and Zn deposition paths in the Zn anode, thus synergistically achieving a bottom‐up deposition behavior for Zn metals and preventing the short circuit from top dendrite growth. As a result, the electrode with triple gradients delivers a low overpotential of 35 mV and operates steadily over 400 h at 5 mA cm‐2/2.5 mAh cm‐2 and 250 h at 10 mA cm‐2/1 mAh cm‐2, far surpassing the non‐gradient, single‐gradient and dual‐gradient counterparts. The well‐tunable materials and structures with the facile fabrication method of the triple‐gradient strategy will bring inspiration for high‐performance energy storage devices.
Identification of the Origin for Reconstructed Active Sites on Oxyhydroxide for Oxygen Evolution Reaction
Authors: Wang Chen , Zhai Panlong , Xia Mingyue , Liu Wei , Gao Junfeng , Sun Licheng , Hou Jungang
Published: November 2022

The regulation of atomic and electronic structures of active sites plays an important role in the rational design of oxygen evolution reaction (OER) catalysts toward electrocatalytic hydrogen generation. However, the precise identification of the active sites for surface reconstruction behavior during OER remains elusive for water‐alkali electrolysis. Herein, irreversible reconstruction behavior accompanied by copper dynamic evolution for cobalt iron layered double hydroxide (CoFe LDH) precatalyst to form CoFeCuOOH active species with high‐valent Co species is reported, identifying the origin of reconstructed active sites through operando UV‐Visible (UV–vis), in situ Raman, and X‐ray absorption fine‐structure (XAFS) spectroscopies. Density functional theory analysis rationalizes this typical electronic structure evolution causing the transfer of intramolecular electrons to form ligand holes, promoting the reconstruction of active sites. Specifically, unambiguous identification of active sites for CoFeCuOOH is explored by in situ 18O isotope‐labeling differential electrochemical mass spectrometry (DEMS) and supported by theoretical calculation, confirming mechanism switch to oxygen‐vacancy‐site mechanism (OVSM) pathway on lattice oxygen. This work enables to elucidate the vital role of dynamic active‐site generation and the representative contribution of OVSM pathway for efficient OER performance.