bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeting intracellular proteins with cell type-specific functions for cancer immunotherapy
Authors: Carelock Madison E , Master Rohan P , Kim Myung-Chul , Jin Zeng , Wang Lei , Maharjan Chandra K , Hua Nan , De Umasankar , Kolb Ryan , Xiao Yufeng , Liao Daiqing , Zheng Guangrong , Zhang Weizhou
Published: May 2023

Immune checkpoint inhibitors (ICIs) use antibodies that block cell surface immune checkpoint proteins with great efficacy in treating immunogenic or “immune hot” tumors such as melanoma, kidney, and lung adenocarcinoma. ICIs have limited response rates to other non-immunogenic cancers. The tumor microenvironment (TME) consists of many cell types that collectively promote tumor progression. Cancer therapeutics are commonly designed to target one molecule in one defined cell type. There is growing evidence that long-term therapeutic responses require the targeting of cancer cells and tumor-promoting populations within the TME. The question remains whether we can identify targetable molecules/pathways that are critical for multiple cell types. Here, we will discuss several molecular targets that may fit a “two or multiple birds, one stone” model, including the B-cell lymphoma-2 (BCL-2) family pro-survival factors, transcriptional factors including signal transducer and activator of transcription 3, the nuclear receptor 4A family (NR4A1, NR4A2, and NR4A3), as well as epigenetic regulators such as bromodomain and extra-terminal (BET) family proteins, histone deacetylase family, SET domain bifurcated histone lysine methyltransferase 1 (SETDB1), and lysine-specific demethylase 1 (LSD1/KDM1A). We will focus on the rationale of these targets in immune modulation, as well as the strategies for targeting these important proteins for cancer therapy.
Caring for Caregivers to Be
Authors: Charney Dennis S.
Published: May 2023

This book provides a scoping summary review of the evidence related to medical student and graduate medical trainee well-being, enabling readers to make use of a variety of tools and instruments believed to have impact on reducing burnout and promoting the development of a resilient and professionally fulfilled physician work force. Areas of focus described within this edited volume include an overview of models and terminology for well-being, the prevalence of burnout and depression in medical trainees, major drivers contributing to burnout and well-being, and the consequences of suboptimal well-being. Using the most current supporting evidence, the book then describes practical considerations for initiating and implementing comprehensive solutions-based well-being programs. Readers will also learn strategies to “make the case” within their organization for directing resources to address medical student and graduate medical trainee well-being, and they can explore opportunities for advocacy in support of well-being at a societal level.
Advocating for Physician Well-Being at the Societal Level
Authors: Sinsky Christine A. , Ristow Alexandra M.
Published: May 2023

This chapter examines the role of advocacy in promoting physician well-being. Addressing physician burnout is a shared responsibility and opportunity. Four levers of advocacy to improve the US health care system’s ability to care for its physicians are explored: research, activation, resources, and workforce demand. Recommendations for research to advance the science of practice that will help improve the clinical environment and thus reduce physician burnout are presented. Examples of activation at the individual, institutional, and national levels are shared. Resources that provide actionable guidance for policy, practice, and leadership changes to support well-being are highlighted. Finally, the power of workforce demand is addressed. Physician burnout is primarily driven by systems factors, so the focus of efforts to improve well-being is on fixing the workplace rather than fixing the worker. The system is broken, not the people within it.
Current landscape of social media use pertaining to glioblastoma by various stakeholders
Authors: Alvi Mohammed Ali , Elkaim Lior M , Levett Jordan J , Pando Alejandro , Roy Sabrina , Samuel Nardin , Alotaibi Naif M , Zadeh Gelareh
Published: May 2023

Background

Given the potential for social media to allow widespread public engagement, its role in healthcare, including in cancer care as a support network, is garnering interest. To date, the use of social media in neuro-oncology has not been systematically explored. In the current manuscript, we sought to review Twitter use on glioblastoma among patients, caregivers, providers, researchers, and other stakeholders.

Methods

The Twitter application programming interface (API) database was surveyed from inception to May 2022 to identify tweets about glioblastoma. Number of tweet likes, retweets, quotes, and total engagement were noted for each tweet. Geographic location, number of followers, and number of Tweets were noted for users. We also categorized Tweets based on their underlying themes. A natural language processing (NLP) algorithm was used to assign a polarity score, subjectivity score, and analysis label to each Tweet for sentiment analysis.

Results

A total of 1690 unique tweets from 1000 accounts were included in our analyses. The frequency of tweets increased from 2013 and peaked in 2018. The most common category among users was MD/researchers (21.6%, n = 216), followed by Media/News (20%, n = 200) and Business (10.7%); patients or caregivers accounted for only 4.7% (n = 47) while medical centers, journals, and foundations accounted for 5.4%, 3.7%, and 2.1%. The most common subjects that Tweets covered included research (54%), followed by personal experience (18.2%) and raising awareness (14%). In terms of sentiment, 43.6% of Tweets were classified as positive, 41.6% as neutral, and 14.9% as negative; a subset analysis of “personal experience” tweets revealed a higher proportion of negative Tweets (31.5%) and less neutral tweets (25%). Only media (β = 8.4; 95% CI [4.4, 12.4]) and follower count (minimally) predicted higher levels of Tweet engagement.

Conclusion

This comprehensive analysis of tweets on glioblastoma found that the academic community are the most common user group on Twitter. Sentiment analysis revealed that most negative tweets are related to personal experience. These analyses provide the basis for further work into supporting and developing the care of patients with glioblastoma.
Ir0/graphdiyne atomic interface for selective epoxidation
Authors: Zheng Zhiqiang , Qi Lu , Gao Yaqi , Luan Xiaoyu , Xue Yurui , He Feng , Li Yuliang
Published: May 2023

The development of catalysts that can selectively and efficiently promote the alkene epoxidation at ambient temperatures and pressures is an important promising path to renewable synthesis of various chemical products. Here we report a new type of zerovalent atom catalysts comprised of zerovalent Ir atoms highly dispersed and anchored on graphdiyne (Ir0/GDY) wherein the Ir0 is stabilized by the incomplete charge transfer effect and the confined effect of GDY natural cavity. The Ir0/GDY can selectively and efficiently produce styrene oxides (SO) by electro-oxidizing styrene (ST) in aqueous solutions at ambient temperatures and pressures with high conversion efficiency of ∼100%, high SO selectivity of 85.5%, and high Faradaic efficiency (FE) of 55%. Experimental and density functional theory (DFT) calculation results show that the intrinsic activity and stability due to the incomplete charge transfer between Ir0 and GDY effectively promoted the electron exchange between the catalyst and reactant molecule, and realized the selective epoxidation of ST to SO. Studies of the reaction mechanism demonstrate that Ir0/GDY proceeds a distinctive pathway for highly selective and active alkene-to-epoxide conversion from the traditional processes. This work presents a new example of constructing zerovalent metal atoms within the GDY matrix toward selective electrocatalytic epoxidation.
Advice to remain active with arm pain reduces disability
Authors: Walker-Bone K , Macfarlane G J , Burton K , McConnachie A M , Zhang R , Jones G T
Published: May 2023

Background

Arm pain is common amongst working-aged adults and causes substantial work disability. The results of a population-based randomized controlled trial (the ARM trial) suggested that advice to remain active reduced disability after 6 months.

Aims

To verify ARM trial results amongst people in paid employment.

Methods

The ARM trial recruited adults with distal arm pain referred for physiotherapy and randomized equally to three groups: wait-listed for physiotherapy (advised to rest); wait-listed for physiotherapy (advised to remain active) or early physiotherapy. The primary outcome was absence of disability at 26 weeks. Secondary analyses were undertaken amongst participants in paid employment.

Results

Amongst 538 trial participants, 347 (64%) were in paid employment, mean age 46.1 years and 47% in manual work. Employed participants were randomized equally to the three arms. Amongst the 271 (78% workers with 26-week data), 43% of those advised to remain active were free from disability, as compared with 37% of those advised to rest. Forty per cent of those who waited for physiotherapy were disability-free as compared with 35% of those treated rapidly. Advice to rest was associated with lower chances of recovery amongst workers who lift/carry weights and those who believed work had caused their symptoms (P = 0.023).

Conclusions

Although not powered as a trial for workers only, our findings suggest that advising activity was as beneficial for people currently in paid work and may be superior to advice to rest in reducing disability. Addressing harmful beliefs about causation of symptoms has the potential to reduce disability.
Very long baseline interferometry imaging of H2O maser emission in the nearby radio galaxy NGC 4261
Authors: Sawada-Satoh Satoko , Kawakatu Nozomu , Niinuma Kotaro , Kameno Seiji
Published: May 2023

We report dual-frequency very long baseline interferometry (VLBI) observations at 22 and 43 GHz toward the nucleus of a nearby radio galaxy NGC 4261. In particular, we present a VLBI image of the 22 GHz H2O maser line and its location in the circumnuclear region of NGC 4261. H2O maser emission is marginally detected above the three times the image rms level at channels within a velocity range of approximately 2250–2450 km s−1, slightly red-shifted with respect to the systemic velocity. H2O maser emission is located approximately 1 milliarcsecond east of the brightest continuum component at 22 GHz, where the continuum spectrum is optically thick, that is, at the free–free absorbed receding jet by ionized gas. A positional coincidence between H2O maser emission and an ionized gas disk implies that the H2O maser emission arises from the near side of the disk, amplifying continuum emission from the background receding jet. If the disk axis is oriented 64° relative to the line of sight, the H2O maser emission is expected to be at a mean radius of 0.3 pc in the disk. The broad line width of the H2O maser emission can be attributed to complex kinematics in the immediate vicinity of the supermassive black hole (SMBH), including ongoing gas infall on to the SMBH, turbulence, and outflow. This is analogous to the multi-phase circumnuclear torus model in the nearest radio-loud H2O megamaser source NGC 1052. An alternative explanation for H2O maser association is the shock region between the jet and ambient molecular clouds. However, this explanation fails to describe the explicit association of H2O maser emission only with the free–free absorbed receding jet.
Current Insights into the Redox Regulation Network in Plant Chloroplasts
Authors: Yoshida Keisuke , Hisabori Toru
Published: May 2023

Thiol/disulfide-based redox regulation is a ubiquitous post-translational protein modification. In plant chloroplasts, this regulatory mechanism is tightly associated with the light-dependent activation of photosynthetic enzymes (e.g. Calvin–Benson cycle enzymes). A thioredoxin (Trx)-mediated pathway was discovered to transmit light signals as a reducing power about half a century ago; since then, it has been accepted as the basic machinery of chloroplast redox regulation. However, during the past two decades, it has been increasingly apparent that plants have acquired multiple Trx isoforms and Trx-like proteins in chloroplasts. Furthermore, proteomics-based analyses have identified various chloroplast enzymes as potential targets of redox regulation. These facts highlight the necessity to revisit the molecular basis and physiological importance of the redox regulation system in chloroplasts. Recent studies have revealed novel aspects of this system, including unprecedented redox-regulated processes in chloroplasts and the functional diversity of Trx family proteins. Of particular significance is the identification of protein-oxidizing pathways that turn off photosynthetic metabolism during light-to-dark transitions. In this review, we summarize current insights into the redox regulation network in chloroplasts.
A Tunisian wild grape leads to metabolic fingerprints of salt tolerance
Authors: Daldoul Samia , Gargouri Mahmoud , Weinert Christoph , Jarrar Ali , Egert Björn , Mliki Ahmed , Nick Peter
Published: May 2023

Soil salinity is progressively impacting agriculture, including viticulture. Identification of genetic factors rendering grapevine (Vitis vinifera L.) resilience that can be introgressed into commercial varieties is necessary for safeguarding viticulture against the consequences of global climate change. To gain insight into the physiological and metabolic responses enabling salt tolerance, we compared a salt-tolerant accession of Vitis sylvestris from Tunisia, “Tebaba”, with “1103 Paulsen” rootstock widely used in the Mediterranean. Salt stress was slowly increased, simulating the situation of an irrigated vineyard. We determined that “Tebaba” does not sequester sodium in the root but can cope with salinity through robust redox homeostasis. This is linked with rechanneling of metabolic pathways toward antioxidants and compatible osmolytes, buffering photosynthesis, such that cell-wall breakdown can be avoided. We propose that salt tolerance of this wild grapevine cannot be attributed to a single genetic factor but emerges from favorable metabolic fluxes that are mutually supportive. We suggest that introgression of “Tebaba” into commercial varieties is preferred over the use of “Tebaba” as a rootstock for improving salt tolerance in grapevine.
Hydrogen peroxide sensor HyPer7 illuminates tissue-specific plastid redox dynamics
Authors: Dopp Isaac J , Kalac Kylie , Mackenzie Sally A
Published: May 2023

The visualization of photosynthesis-derived reactive oxygen species has been experimentally limited to pH-sensitive probes, unspecific redox dyes, and whole-plant phenotyping. Recent emergence of probes that circumvent these limitations permits advanced experimental approaches to investigate in situ plastid redox properties. Despite growing evidence of heterogeneity in photosynthetic plastids, investigations have not addressed the potential for spatial variation in redox and/or reactive oxygen dynamics. To study the dynamics of H2O2 in distinct plastid types, we targeted the pH-insensitive, highly specific probe HyPer7 to the plastid stroma in Arabidopsis (Arabidopsis thaliana). Using HyPer7 and glutathione redox potential (EGSH) probe for redox-active green fluorescent protein 2 genetically fused to the redox enzyme human glutaredoxin-1 with live cell imaging and optical dissection of cell types, we report heterogeneities in H2O2 accumulation and redox buffering within distinct epidermal plastids in response to excess light and hormone application. Our observations suggest that plastid types can be differentiated by their physiological redox features. These data underscore the variation in photosynthetic plastid redox dynamics and demonstrate the need for cell-type-specific observations in future plastid phenotyping.
Cell signaling in the shoot apical meristem
Authors: Wang Ying , Jiao Yuling
Published: May 2023

Distinct from animals, plants maintain organogenesis from specialized tissues termed meristems throughout life. In the shoot apex, the shoot apical meristem (SAM) produces all aerial organs, such as leaves, from its periphery. For this, the SAM needs to precisely balance stem cell renewal and differentiation, which is achieved through dynamic zonation of the SAM, and cell signaling within functional domains is key for SAM functions. The WUSCHEL-CLAVATA feedback loop plays a key role in SAM homeostasis, and recent studies have uncovered new components, expanding our understanding of the spatial expression and signaling mechanism. Advances in polar auxin transport and signaling have contributed to knowledge of the multifaceted roles of auxin in the SAM and organogenesis. Finally, single-cell techniques have expanded our understanding of the cellular functions within the shoot apex at single-cell resolution. In this review, we summarize the most up-to-date understanding of cell signaling in the SAM and focus on the multiple levels of regulation of SAM formation and maintenance.
Deadly Debt Crises: COVID-19 in Emerging Markets
Authors: Arellano Cristina , Bai Yan , Mihalache Gabriel
Published: May 2023

Emerging markets have experienced large human and economic costs from coronavirus disease 2019, and their tight fiscal space has limited the support extended to their citizens. We study the impact of an epidemic on economic and health outcomes by integrating epidemiological dynamics into a sovereign default model. The sovereign’s option to default tightens fiscal space and results in an epidemic with limited mitigation and depressed consumption. A quantitative analysis of our model accounts well for the dynamics of fatalities, social distancing, consumption, sovereign debt, and spreads in Latin America. We find that because of default risk, the welfare cost of the pandemic is about a third higher than it is in a version of the model with perfect financial markets. We study debt relief programs and find a compelling case for their implementation. These programs deliver large social gains, improving health and economic outcomes for the country at no cost to international lenders or financial institutions.
Implications of the accuracy of diagnostic algorithms for systemic lupus on our understanding of racial disparities in pregnancy outcomes
Authors: Clowse Megan E B , Oates James , Barnado April , Kirchoff Katie , Blaske Ashley , Sheikh Saira Z , Crofford Leslie J , Eudy Amanda M
Published: May 2023

Objective

Disparities in pregnancy outcomes among women with SLE remain understudied, with few available racially diverse datasets. We sought to identify disparities between Black and White women in pregnancy outcomes within academic institutions in the United States.

Methods

Using the Common Data Model electronic medical record (EMR)-based datasets within the Carolinas Collaborative, we identified women with pregnancy delivery data (2014–2019) and ≥1 SLE International Classification of Diseases 9 or 10 code (ICD9/10) code. From this dataset, we identified four cohorts of SLE pregnancies, three based on EMR-based algorithms and one confirmed with chart review. We compared the pregnancy outcomes identified in each of these cohorts for Black and White women.

Results

Of 172 pregnancies in women with ≥1 SLE ICD9/10 code, 49% had confirmed SLE. Adverse pregnancy outcomes occurred in 40% of pregnancies in women with ≥1 ICD9/10 SLE code and 52% of pregnancies with confirmed SLE. SLE was frequently over-diagnosed in women who were White, resulting in 40–75% lower rates of adverse pregnancy outcomes in EMR-derived vs confirmed SLE cohorts. Over-diagnosis was less common for Black women with pregnancy outcomes 12–20% lower in EMR-derived vs confirmed SLE cohorts. Black women had higher rates of adverse pregnancy outcomes than White women in the EMR-derived, but not the confirmed cohorts.

Conclusion

EMR-derived cohorts of pregnancies in women who are Black, but not White, provided accurate estimations of pregnancy outcomes. The data from the confirmed SLE pregnancies suggest that all women with SLE, regardless of race, referred to academic centres remain at very high risk for adverse pregnancy outcome.
The issue of Cs-137 in firewood and biomass combustion: a review
Authors: Pepin Stéphane , Radulovic Sarah , Wiegers Rob , Mrdakovic Popic Jelena , Kallio Antti , Huss Marie , Grandia Fidel , Valls Alba , Bruno Aina
Published: May 2023

In large parts of Europe, the Chernobyl accident of 1986 caused fallout of Cs-137. This led to the uptake of Cs-137 in trees or other materials used for bioenergy production or as firewood for domestic purposes. This Cs-137 may concentrate in the ashes of the combustion process in such a way that the clearance level of 100 Bq per kg, defined in Directive 2013/59/Euratom (EU BSS), may consequently be exceeded. There is currently no clear consensus in Europe regarding the regulatory approach to this issue: should the import and use of Cs-137 contaminated biomass and its ashes be considered as a planned exposure situation or rather as an existing exposure situation? If considered as an existing exposure situation, which reference level should be applied? We compare the approaches in various European countries, such as Finland, Norway, Sweden, Belgium and the Netherlands. Results of a recent measurement campaign performed in Belgium on firewood imported from Belarus, Ukraine and other countries show a quite large range of Cs-137 activity concentration in firewood. Analysis of samples from biomass combustion confirms that the clearance level of 100 Bq per kg Cs-137 may be exceeded even when the activity concentration in the initial pellet is trivial. A review of dose-assessment studies performed by STUK and from the literature is presented. The general context of biomass energy production is sketched: for instance, in the Netherlands, 40 large biomass firing plants (capacity > 10 MW) are operational and some 20 more are already planned. The fly ashes from the biomass combustion may be a valuable resource for the construction industry, and the issue of Cs-137 contamination is connected with the requirements of the EU BSS regarding the natural radioactivity of building materials. Assessing the impact of Cs-137 contamination and clarifying regulations in the frame of a graded approach are important elements in this context.
Radiation protection challenges in the upgrade, autopsy and disposal of the LHC beam dump
Authors: Infantino Angelo , Bernardes Ana-Paula , Calviani Marco , Dumont Gerald , El-Idrissi Safouane , Mouret Renaud , Tromel Christophe , Vincke Heinz
Published: May 2023

The upgrade of the Large Hadron Collider spare beam dumps (Target Dump External, TDE) and the autopsy of the old operational TDE required to perform several activities in a high-radiation environment posing significant radiation protection challenges due to the residual activation of the equipment. To ensure high safety standards and to respect the ALARA principle, these challenges were addressed using the advanced Monte Carlo techniques to predict the residual ambient dose equivalent rate and the radionuclide inventory at different steps of the interventions. The CERN HSE-RP group makes extensive use of the FLUKA and ActiWiz codes to produce accurate estimates. This work aims to provide an overview of the radiation protection studies to optimise the interventions (ALARA) and to reduce the radiological risk for personnel and environment.
Radiation protection challenges for the Large Hadron Collider upgrade
Authors: Elie Lucie , Dyrcz Patrycja , Infantino Angelo , Tromel Christophe , Vincke Heinz
Published: May 2023

In the context of the so-called Long Shutdown 3 (2026–2028), the Large Hadron Collider will be upgraded to the High-Luminosity Large Hadron Collider, allowing for approximately five more instantaneous collisions. The upgrade, maintenance and decommissioning of equipment will be mainly performed in the experimental insertions of Points 1 and 5, requiring to perform multiple interventions in high-residual radiation environment. This poses complex radiological challenges that the CERN Radiation Protection group is called to address. Radiation protection studies are performed to plan and optimise (ALARA) these future interventions using the advanced Monte Carlo techniques and tools such as FLUKA, ActiWiz, SESAME and the FCC method. This paper aims to provide an overview of the studies conducted to estimate the residual radiation field in the experimental insertions, the activation levels in terms of multiple of the Swiss clearance limits/specific activity and to provide preliminary considerations on the upgrade/decommissioning of key equipment.
Strengths of ecosystem services concept for radiation protection
Authors: Beauquier Sophie , Gilbin Rodolphe , Billarand Yann , Bonzom Jean-Marc , Radakovitch Olivier , Goni Felipe Ramirez , Simon-Cornu Marie
Published: May 2023

The successful ecosystem services concept, defined as the benefits people obtain from ecosystems is still not really reflected in the current approaches for protecting public and environment against radiation promoted by the International Commission on Radiological Protection or other similar approaches. Yet some recent thoughts from international organizations lead us to believe that an eco-based approach could be more promoted in the coming years in environmental radiation protection field. The French Institute for Radiation Protection and Nuclear Safety has identified different fields of application of this concept into radiation protection, in line with its integrated approach of radiological risks management. As the ecosystem services approach makes it possible to highlight biophysical and socio-economic approaches of the impacts of ionizing radiation on ecosystems, it represents a subject of primary importance for future works conducted by IRSN. However, the operationality of the ecosystem services concept is the subject of many debates. In many situations, scientists have not yet fully understood how radioactive contamination could affect ecosystem services, and how to articulate with certainty cause and effect relationships between state of an ecosystem and provision of services. In addition, the concept is also accompanied by contradictory perceptions of the status of humans in ecosystems. To solve these knowledge gaps and uncertainties, it is necessary to acquire robust data on the impacts of radiation on ecosystems both under experimental and realistic conditions, and to integrate all potential consequences (direct and indirect, ecotoxicological but also economic and cultural).
Introduction: Marking Race in Twentieth Century British History
Authors: Matera Marc , Natarajan Radhika , Perry Kennetta Hammond , Schofield Camilla , Waters Rob
Published: May 2023

How might historians narrate Britain’s past if we centre imperial racial formation and its contestations? The thirtieth anniversary of Paul Gilroy’s There Ain’t No Black in the Union Jack: The Cultural Politics of Race and Nation provided an opportunity for a new generation of scholars to consider the frameworks of race in British history. In 1987, Gilroy challenged Marxist approaches that treated race as secondary to or even a mechanistic expression of class inequality. He showed that the failure to account for race and empire positioned racialized subjects as perpetual outsiders. Taking up Gilroy’s analysis as a point of departure, this thematic issue brings together analyses of the state, institutions, and individuals to propose new periodizations, geographies, and methodologies for understanding twentieth-century British history. In this introduction, Marc Matera, Radhika Natarajan, Kennetta Hammond Perry, Camilla Schofield, and Rob Waters describe the five-year conversation that led to this thematic issue, introduce their respective essays, and explain why race must be understood not as a descriptive category but as an analytical framework for understanding Britain’s past.
Use of the dTAG system in vivo to degrade CDK2 and CDK5 in adult mice and explore potential safety liabilities
Authors: Yenerall Paul , Sung Tae , Palyada Kiran , Qian Jessie , Arat Seda , Kumpf Steven W , Wang Shih-Wen , Biddle Kathleen , Esparza Carlos , Chang Stephanie , Scott Wesley , Collette Walter , Winrow Taylor-Symon , Affolter Tim , Shirai Norimitsu , Thibault Stephane , Wang Julia , Liu Ling , Bauchmann Mary , Frey Jessica , Steyn Stefanus , Sacaan Aida , Vitsky Allison , Ahn Youngwook , Paul Tom , Lum Lawrence , Oyer Jon , Yang Amy , Hu Wenyue
Published: May 2023

The degradation tag (dTAG) system for target protein degradation can remove proteins from biological systems without the drawbacks of some genetic methods, such as slow kinetics, lack of reversibility, low specificity, and the inability to titrate dosage. These drawbacks can make it difficult to compare toxicity resulting from genetic and pharmacological interventions, especially in vivo. Because the dTAG system has not been studied extensively in vivo, we explored the use of this system to study the physiological sequalae resulting from CDK2 or CDK5 degradation in adult mice. Mice with homozygous knock-in of the dTAG sequence onto CDK2 and CDK5 were born at Mendelian ratios despite decreased CDK2 or CDK5 protein levels in comparison with wild-type mice. In bone marrow cells and duodenum organoids derived from these mice, treatment with the dTAG degrader dTAG-13 resulted in rapid and robust protein degradation but caused no appreciable change in viability or the transcriptome. Repeated delivery of dTAG-13 in vivo for toxicity studies proved challenging; we explored multiple formulations in an effort to maximize degradation while minimizing formulation-related toxicity. Degradation of CDK2 or CDK5 in all organs except the brain, where dTAG-13 likely did not cross the blood brain barrier, only caused microscopic changes in the testis of CDK2dTAG mice. These findings were corroborated with conditional CDK2 knockout in adult mice. Our results suggest that the dTAG system can provide robust protein degradation in vivo and that loss of CDK2 or CDK5 in adult mice causes no previously unknown phenotypes.
Brachyury positively regulates extracellular matrix synthesis via directly promoting aggrecan transcription in nucleus pulposus
Authors: Wu Yinghui , Xia Yanzhang , Yue Caichun , Xin Tianwen , Wang Qiang , Zhang Hong , Shen Cong , Shen Minghong , Gu Yao , Shen Jun
Published: May 2023

Nucleus pulposus (NP) degeneration is characterized by the decreased cellularity of nucleus pulposus cells (NPCs) and diminished content of hydrophilic extracellular matrix (ECM). Overexpression of brachyury has been reported to reverse the degenerated NPCs into healthy phenotypes. However, the direct correlation between brachyury and ECM has not been fully elucidated. This study revealed that brachyury expression decreased in human degenerated NP tissues and Lipopolysaccharide (LPS)‐induced degenerated rat NPCs model. In vitro and in vivo experiments further showed that brachyury deficiency suppressed the synthesis of aggrecan and collagen II in NP. Mechanistically, ChIP‐qPCR assays demonstrated that brachyury bound to the promoter region of aggrecan in NPCs. Furthermore, luciferase reporter assays revealed that brachyury transcriptionally activated aggrecan expression through binding with a novel specific motif. In rat in vivo model, brachyury overexpression partially reversed the degenerative phenotype. In conclusion, brachyury positively regulated ECM synthesis via directly promoting aggrecan transcription in NPCs. Accordingly, it may be helpful to be developed into a promising therapeutic target for NP degeneration.
Nursing Informatics
Authors: Ulanday Kathleen
Published: May 2023

These nurses leverage technology to improve health.
Supporting the Health and Well-Being of Caregivers of Persons with Pain
Authors: Tonkikh Orly , Chi Nai-Ching , Herr Keela A. , Fishman Scott M. , Young Heather M.
Published: May 2023

This article is part of a series, Supporting Family Caregivers: No Longer Home Alone, published in collaboration with the AARP Public Policy Institute. Results of focus groups, conducted as part of the AARP Public Policy Institute's No Longer Home Alone video project, supported evidence that family caregivers aren't given the information they need to manage the complex care regimens of family members. This series of articles and accompanying videos aims to help nurses provide caregivers with the tools they need to manage their family member's health care at home.

This new group of articles provides practical information nurses can share with family caregivers of persons living with pain. To use this series, nurses should read the articles first, so they understand how best to help family caregivers. Then they can refer caregivers to the informational tear sheet—Information for Family Caregivers—and instructional videos, encouraging them to ask questions. For additional information, see Resources for Nurses.
DNA methyltransferase inhibitor 5-azacytidine enhances neuroblastoma cell lysis by an oncolytic parainfluenza virus
Authors: Kedarinath Kritika , Shiffer Elisabeth M. , Parks Griffith D.
Published: May 2023

Studies with neuroblastoma have shown that the presence of aberrant DNA epigenetic modifications mediated by DNA methyltransferases correlates with poor prognosis, making these enzymes a target for therapeutics based on synthetic epigenetic modulators such as DNA methyltransferase inhibitors (DNMTi). Here, we have used a neuroblastoma cell line model to test the hypothesis that treatment with a DNMTi would enhance cell killing when used in combination with oncolytic Parainfluenza virus 5 (P/V virus), a cytoplasmic-replicating RNA virus. Pretreatment of SK-N-AS cells with the DNMTi 5-azacytidine substantially enhanced P/V virus-mediated cell death in a dose- and multiplicity of infection-dependent manner. Infection with the virus alone and the combination treatment with 5-azacytidine and P/V virus infection led to the activation of caspases-8, -9, and -3/7. Inhibition of caspases using a pan-caspase inhibitor minimally affected cell killing by P/V virus alone, but by contrast, largely reduced cell death mediated by 5-azacytidine treatment alone or in combination with P/V virus infection. 5-Azacytidine pretreatment dampened P/V virus gene expression and growth within the SK-N-AS cell population, which correlated with enhanced expression of important antiviral genes such as interferon-β and OAS2. Taken together, our data support the role of combination treatment using 5-azacytidine and an oncolytic P/V virus for neuroblastoma therapy.
The Relationship Between Compassion Fatigue and Nursing Care Quality in Intensive Care Units
Authors: Abedian Nafiseh , Khoddam Homeira , Kolagari Shohreh
Published: May 2023

Intensive care unit (ICU) nurses are repetitively exposed to traumatic situations and stressful events, which can lead to compassion fatigue (CF). Compassion fatigue can negatively affect the nurses' emotional and physical health and job satisfaction. The aim of this study was to evaluate the relationship between CF and nursing care quality in ICU. This descriptive-correlational study was conducted on 46 ICU nurses and 138 ICU patients, in 2 referral hospitals in Gorgan, Northeast of Iran in 2020. Participants were selected using stratified random sampling. Data were collected using CF and nursing care quality questionnaires. The results of this study showed that most nurses were women (n = 31, 67.4%), with mean age of 28.58 ± 4.80 years. The mean patients' age was 49.22 ± 22.01 years and 87 (63%) of them were male. The severity of CF in most ICU nurses (54.3%) was moderate, with a mean score of 86.21 ± 16.78. Among of the subscales, psychosomatic score was higher than the rest of subscales (0.53 ± 0.26). Nursing care quality was at the optimal level (91.3%) with the mean score of 81.51 ± 9.93. The highest scores of nursing care were related to subscale of medications, intake, and output (0.92 ± 0.23). In this study, there was a weak and inverse relationship between CF and nursing care quality (r = −0.28; P = .058). The results of this study indicate a weak, nonsignificant inverse relationship between CF and nursing care quality in ICU.
The Arrhythmogenicity of Sotalol and its Role in Heart Failure: A Literature Review
Authors: Augustin Najwan , Alvarez Chikezie , Kluger Jeffrey
Published: May 2023

According to the American Heart Association, approximately 6 million adults have been afflicted with heart failure in the United States in 2020 and are more likely to have sudden cardiac death accounting for approximately 50% of the cause of mortality. Sotalol is a nonselective β-adrenergic receptor antagonist with class III antiarrhythmic properties that has been mostly used for atrial fibrillation treatment and suppressing recurrent ventricular tachyarrhythmias. The use of sotalol in patients with left ventricular dysfunction is not recommended by the American College of Cardiology or American Heart Association because studies are inconclusive with conflicting results regarding safety. This article aims to review the mechanism of action of sotalol, the β-blocking effects on heart failure, and provide an overview of clinical trials on sotalol use and its effects in patients with heart failure. Small- and large-scale clinical trials have been controversial and inconclusive about the use of sotalol in heart failure. Sotalol has been shown to reduce defibrillation energy requirements and reduce shocks from implantable cardioverter-defibrillators. Torsades de Pointes is the most life-threatening arrhythmia that has been documented with sotalol use and occurs more commonly in women and heart failure patients. Thus far, mortality benefits have not been demonstrated with sotalol use and larger multicenter studies are required going forward.
Applying the 2022 Cardiovascular and Pulmonary Entry-Level Physical Therapist Competencies to Physical Therapist Education and Practice
Authors: Smith Nancy , Campbell Angela , Johanson Morgan , Bartlo Pamela , Bauer Naomi , Everett Sagan
Published: May 2023

Background and Purpose.

Competency-based education (CBE) is an emerging topic within physical therapy (PT). It has emerged to assure all stakeholders that physical therapist education program graduates are proficient in the requisite knowledge, skills, and behaviors (KSBs) essential for entry-level practice. Competencies have existed within cardiovascular and pulmonary (CVP) PT since 1980, updated in 2008, and most recently updated in 2022. This article discusses how individuals should apply the 2022 CVP competencies to clinical practice and education.

Position and Rationale.

The 2022 CVP competencies were developed using a modified mixed-method Delphi approach. These competencies set a level of proficiency for KSBs used within entry-level CVP PT practice following the patient–client management model. The position put forward in this article describes how and why multiple stakeholder groups should apply these entry-level competencies specifically for graduates of physical therapist education programs who are entering practice (entry level). The competencies provide a more detailed description of expected proficiency for entry-level CVP PT practice than currently available documents. These competencies may form the basis for developing entrustable professional activities (EPAs).

Discussion and Conclusion.

The establishment of entry-level competencies is essential for use by multiple stakeholders to inform physical therapist curriculum, provide clinical instructors with a reference for expected levels of proficiency during final student clinical experiences, guide content on the Federation of State Boards of PT national licensure examination, and prepare employers to provide needed continued professional development, based on the clinical environment. These competencies lend themselves to the future development of EPAs in the PT profession for CVP PT.
Using an individualized pain management plan for African American adults with sickle cell disease
Authors: Macey-Stewart Karen V. , Louie Kem
Published: May 2023

Background.

The increased lifespan of individuals having sickle cell disease (SCD) causes an overall increase in hospitalizations and more instances in which pain may not be well controlled.

Local problem.

The mainstay treatment for severe pain is opioids and the underlying cause. Laws affecting opioid prescribing, implicit bias, racial inequity, poor research funding, and lack of knowledge contribute to poor patient outcomes.

Method.

Data were collected retrospectively using electronic medical record data from before and after the intervention.

Intervention.

The individualized pain management plan (IPMP) was initiated in collaboration with the patient, pain nurse practitioner (NP), and hematologist.

Result.

The mean length of stay for the traditional pain management plan (TPMP) was 7.89 days compared with 5.66 days for the IPMP, with a mean difference of 2.23 days, t = 2.278, p = .024 (p < .05). There was a decrease in the admission of the individuals with the IPMP, with 25% readmitted within 30 days of discharge, versus 59.0% who were readmitted using the TPMP. Chi-square showed statistical significance (χ2 = 61.667, p = .000) in using nonpharmacological interventions with the IPMP group.

Conclusion.

The IPMP with a patient-centered approach did improve patient outcomes for African American adults living with SCD.
Use of Virtual Reality Simulations to Embody a Patient
Authors: Flood Lisa Sue
Published: May 2023

Background:

Using immersive virtual reality (VR), students are able to physically and emotionally embody patients while interacting in simulated environments with family and health care providers.

Purpose:

This pilot study explored how embodying patients with Alzheimer disease and terminal cancer at end of life using highly immersive VR impacted nursing students' confidence, feelings, and perceptions.

Methods:

A quasi-experimental design was used with a convenience sample of bachelor of science in nursing students who completed pre/posttest scaled and open-ended questions.

Results:

Participants (N = 32) reported significant confidence increases; feelings about dying and hospice were also significantly changed. The majority described how the simulations would impact their future nursing care.

Conclusion:

Using VR, students experienced disease, dying, and health care from the patient's perspective reporting differences in confidence, feelings, and perceptions. Immersive VR simulations warrant further study and have the potential to transform nursing education and impact health care.
How much do young Australians know about syphilis compared with chlamydia and gonorrhoea? Findings from an online survey
Authors: Bittleston Helen , Goller Jane L. , Temple-Smith Meredith , Coombe Jacqueline , Hocking Jane S.
Published: May 2023

Background

There is increased heterosexual transmission of syphilis in Australia, an infection with severe outcomes. Australian policy emphasises increasing sexually transmissible infection (STI) knowledge/awareness. However, little is known about young Australians’ perceptions and knowledge of syphilis.

Methods

Our online sexual health survey was open 2nd May–21st June 2022 to 16-29-year-olds in Australia. We asked participants if they were aware of syphilis, their personal risk perception, and perceived severity of infection and compared to results for chlamydia/gonorrhoea. Multivariable and multinomial logistic regression was used to assess characteristics associated with outcomes. We measured STI knowledge using ten true/false statements (five syphilis, five chlamydia/gonorrhoea).

Results

Among 2018 participants (69.1% women, 48.9% heterosexual), 91.3% had heard of syphilis (versus 97.2% for chlamydia and 93.3% for gonorrhoea). Older (25-29 years aOR = 2.4, 95%CI 1.4-4.4) and gay/lesbian (aOR = 2.8, 95%CI 1.4-5.3) respondents were more likely to have heard of syphilis, as were those who were non-Aboriginal, sexually active, and with a school-based sex education. Syphilis knowledge was lower than chlamydia/gonorrhoea knowledge (p < 0.001). 59.7% perceived syphilis to have serious health impacts (versus 36.4% for chlamydia and 42.3% for gonorrhoea). Older respondents were more likely (25-29 years aOR 2.1, 95%CI 1.6-2.8), and gay/lesbian respondents less likely (aOR 0.7, 95%CI 0.6-1.0) to perceive syphilis to have serious health impacts. One-fifth of sexually active participants were unsure of their risk of syphilis.

Conclusions

Most young Australians are aware of syphilis, but few have comprehensive knowledge about the infection relative to chlamydia/gonorrhoea. Considering increasing heterosexual transmission, syphilis health promotion campaigns should expand their focus.
Simplified lung ultrasound method to predict the respiratory support needs of neonates whose mothers had pregnancy complications: a diagnostic accuracy study
Authors: Lin Xin-Ao , Wang Xue-Feng , Fan Xiao-Bo , Xi Guan-Nan , Wang Ji-Mei
Published: May 2023

Objective:

Some pregnancy complications are associated with respiratory problems in infants. Early identification and implementation of respiratory support are needed for these infants. This study aimed to (1) use lung ultrasound (LU) for predicting the respiratory support requirements of infants and (2) simplify the examination method to facilitate its clinical application.

Methods:

Neonates underwent LU examinations within 1 hour of birth. The infants were divided into a pregnancy complication (PC) group and a control group according to their mothers’ clinical data. The primary outcome measure was the need for respiratory support. Predictive models were established based on the differences in LU patterns between the two groups. The predictive value of the models was compared with that of the LU score (LUS) system, which has been widely used in other studies. Simplified models were established by analyzing the predictive effects of LU patterns in different parts of the lungs. Predictive reliability was tested using the receiver operating characteristic curve analysis.

Results:

PC and control groups had 29 and 117 neonates, respectively; a total of 22 neonates required respiratory support. The PC and control groups showed differences in respiratory support requirements, A-lines, and coalesced B-lines. The percentages of A-lines and coalesced B-lines were associated with respiratory support requirements. The optimal cutoff values for the percentages of the A-lines and coalesced B-lines were 55.7% and 24.5%, respectively. Similar effects were obtained by calculating the percentage of coalesced B-lines in four areas (R3, R4, L3, and L4). These methods were judged as more visual and convenient than LUS assessment.

Conclusion:

The percentages of A-line and coalesced B-lines on LU images can be used to predict the respiratory support needs of neonates whose mothers had pregnancy complications. Only four areas (R3, R4, L3, and L4) had similar predictive values.