bluuebunny/crossref_metadata_2025 huggingface dataset:
Interpretable deep residual network uncovers nucleosome positioning and associated features
Authors: Masoudi-Sobhanzadeh Yosef , Li Shuxiang , Peng Yunhui , Panchenko Anna R
Published: July 2024

Nucleosomes represent elementary building units of eukaryotic chromosomes and consist of DNA wrapped around a histone octamer flanked by linker DNA segments. Nucleosomes are central in epigenetic pathways and their genomic positioning is associated with regulation of gene expression, DNA replication, DNA methylation and DNA repair, among other functions. Building on prior discoveries that DNA sequences noticeably affect nucleosome positioning, our objective is to identify nucleosome positions and related features across entire genome. Here, we introduce an interpretable framework based on the concepts of deep residual networks (NuPoSe). Trained on high-coverage human experimental MNase-seq data, NuPoSe is able to learn sequence and structural patterns associated with nucleosome organization in human genome. NuPoSe can be also applied to unseen data from different organisms and cell types. Our findings point to 43 informative features, most of them constitute tri-nucleotides, di-nucleotides and one tetra-nucleotide. Most features are significantly associated with the nucleosomal structural characteristics, namely, periodicity of nucleosomal DNA and its location with respect to a histone octamer. Importantly, we show that features derived from the 27 bp linker DNA flanking nucleosomes contribute up to 10% to the quality of the prediction model. This, along with the comprehensive training sets, deep-learning architecture, and feature selection method, may contribute to the NuPoSe's 80–89% classification accuracy on different independent datasets.
A UTP3-dependent nucleolar translocation pathway facilitates pre-rRNA 5′ETS processing
Authors: Bao Jiayang , Su Baochun , Chen Zheyan , Sun Zhaoxiang , Peng Jinrong , Zhao Shuyi
Published: July 2024

The ribosome small subunit (SSU) is assembled by the SSU processome which contains approximately 70 non-ribosomal protein factors. Whilst the biochemical mechanisms of the SSU processome in 18S rRNA processing and maturation have been extensively studied, how SSU processome components enter the nucleolus has yet to be systematically investigated. Here, in examining the nucleolar localization of 50 human SSU processome components, we found that UTP3, together with another 24 proteins, enter the nucleolus autonomously. For the remaining 25 proteins we found that UTP3/SAS10 assists the nucleolar localization of five proteins (MPP10, UTP25, EMG1 and the two UTP-B components UTP12 and UTP13), likely through its interaction with nuclear importin α. This ‘ferrying’ function of UTP3 was then confirmed as conserved in the zebrafish. We also found that knockdown of human UTP3 impairs cleavage at the A0-site while loss-of-function of either utp3/sas10 or utp13/tbl3 in zebrafish causes the accumulation of aberrantly processed 5′ETS products, which highlights the crucial role of UTP3 in mediating 5′ETS processing. Mechanistically, we found that UTP3 facilitates the degradation of processed 5′ETS by recruiting the RNA exosome component EXOSC10 to the nucleolus. These findings lay the groundwork for studying the mechanism of cytoplasm-to-nucleolus trafficking of SSU processome components.
A Qualitative Study to Understand the Barriers and Facilitators in Smoking Cessation Practices Among Oncology Health Care Practitioners in One Health System
Authors: Frazer Kate , Bhardwaj Nancy , Fox Patricia , Lyons Ailsa , Syed Shiraz , Niranjan Vikram , McCann Amanda , Kelly Catherine , Brennan Sinead , Brennan Donal , Geraghty James , Keane Michael P , Fitzpatrick Patricia
Published: July 2024

Introduction

Despite the benefits of quitting smoking for those who have cancer, including improved health outcomes and reduced therapeutic toxicities, it is unclear how many people are supported in quit attempts during this time. Variations in the availability and provision of smoking cessation (SC) services are reported, with little understanding of the challenges and solutions. This codesigned study aimed to understand the perspectives of health care professionals (HCPs) working in oncology settings to engage in SC practices and identify recommendations for developing a SC pathway.

Aims and Methods

This was a qualitative study. Eighteen HCPs participated in semi-structured interviews from July 2021 to May 2022. We used thematic analysis approaches to code data and present four themes and SC strategies at micro, meso, and organizational levels.

Results

Four themes are reported specifically: (1) timing and knowledge, (2) building a relationship, (3) frequent asking with infrequent action, and (4) removing the barriers and tailoring the system. While HCPs discuss SC, there are variations in documentation and when conversations occur. Primarily, HCPs value the time to build therapeutic relationships with patients and thus may limit SC discussions in preference to treatment in clinical interactions. The role of structural barriers, including prescriptive authority for nurses, hinders active SC processes, as it is the lack of continuity and embedding of services supported by a clinical champion for SC.

Conclusions

The study suggests reevaluating the status quo in SC service, highlighting service gaps, and suggesting opportunities at organizational levels to reduce structural barriers.

Implications

Variations in SC services exist in designated cancer centers. The data from this study can be used to inform a real-time health systems approach for SC services in oncology settings. Developing tailored SC services and interventions that are patient-centered and informed by their experiences is required. The data in this study suggest developing specialist education and training to upskill HCPs for equitable engagement if we are to meet EU and Cancer Moonshot goals for cancer reduction.
Effects of Hesperidin Supplementation on Cardiometabolic Markers: A Systematic Review and Meta-analysis of Randomized Controlled Trials
Authors: Heidari Zeinab , Farahmandpour Fatemeh , Bazyar Hadi , Pashayee-Khamene Fereshteh
Published: July 2024

Context

Hesperidin is a naturally occurring bioactive compound that may influence cardiometabolic markers, but the existing evidence is inconclusive.

Objective

This study aims to further investigate the effects of hesperidin supplementation on cardiometabolic markers in adults.

Data Sources

A comprehensive search was conducted up to August 2023, utilizing relevant key words in databases such as PubMed, Scopus, Embase, and the Cochrane Central Register of Controlled Trials, focusing on randomized controlled trials (RCTs).

Data Extraction

RCTs that examined the impact of hesperidin on fasting blood sugar (FBS), insulin, quantitative insulin-sensitivity check index (QUICKI), homeostatic model assessment of insulin resistance (HOMA-IR), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), systolic blood pressure (SBP), diastolic blood pressure (DBP), tumor necrosis factor-alpha (TNF-α), and high-sensitivity C-reactive protein (hs-CRP) were selected independently by 2 authors. The GRADE assessment was used to ascertain the certainty of the evidence. Results were pooled using a random-effects model as weighted mean differences and 95% CIs.

Data Analysis

The results of this study demonstrate that hesperidin supplementation had a significant impact on reducing FBS, TG, TC, LDL-C, SBP, and TNF-α. However, there was no significant effect observed on insulin, HOMA-IR, QUICKI, HDL-C, DBP, and hs-CRP. The study's subgroup analyses also revealed that interventions lasting more than 12 weeks were effective in reducing FBS, TG, TC, and LDL-C. Moreover, hesperidin dosage exceeding 500 mg/day showed significance in reducing FBS, TC, and LDL-C levels.

Conclusion

In conclusion, this research suggests that hesperidin can be consumed as an effective dietary approach to enhance cardiometabolic markers.

Systematic Review Registration

PROSPERO registration no. CRD42022325775.
Les soins peau-à-peau chez les nourrissons à terme et prématurés
Authors: Altit Gabriel , Hamilton Danica , O’Brien Karel
Published: July 2024

Les soins peau-à-peau (SPP) sont un aspect important des soins au parent et au nourrisson pendant la période néonatale et la première enfance. Ils doivent être entrepris immédiatement après la naissance et faire partie des soins standards dans tous les milieux, y compris à la maison. Selon de solides données probantes, les SPP ont un effet positif sur l’allaitement et l’alimentation par du lait humain, tant chez les nourrissons à terme que prématurés, de même que sur la mortalité, la stabilité cardiorespiratoire et la thermorégulation. Les SPP réduisent la douleur et le stress chez les nourrissons, accroissent l’attachement entre le parent et son nourrisson et ont des effets bénéfiques sur le neurodéveloppement de l’enfant ainsi que sur la santé mentale des parents. Le caractère sécuritaire et la faisabilité des SPP sont établis chez les nourrissons à terme et prématurés, et ces soins sont recommandés dans le cadre d’une pratique exemplaire auprès de tous les nourrissons. Les avantages des SPP sont supérieurs aux risques dans la plupart des situations, et malgré les défis qui y sont associés, les dispensateurs de soins devraient adopter des protocoles et prévoir des adaptations pour s’assurer que les SPP soient une expérience positive et sécuritaire pour le parent, la famille, le nourrisson et l’équipe soignante. Le présent document de principes s’adresse à toutes les familles, telles qu’elles se définissent et se déterminent elles-mêmes, et tiennent compte de l’importance de personnaliser la communication, le langage et la terminologie en matière de santé pour que l’équipe soignante réponde aux besoins particuliers de la famille.
Skin-to-skin care (SSC) for term and preterm infants
Authors: Altit Gabriel , Hamilton Danica , O’Brien Karel
Published: July 2024

Skin-to-skin care (SSC) is an important part of parent and infant care during the neonatal period and into infancy. SSC should be initiated immediately after birth and practiced as a standard of care in all settings, as well as in the home. There is strong evidence that SSC has a positive effect on breastfeeding and human milk feeding in both term and preterm infants, as well as on mortality, cardiopulmonary stability, and thermoregulation. SSC reduces pain and infant stress, enhances parent–infant bonding, has neurodevelopmental benefits, and has positive effects on parental mental health. The safety and feasibility of providing SSC has been established in term and preterm infants, and SSC is recommended as best practice for all infants. The benefits of SSC outweigh the risks in most situations, and despite challenges, care providers should implement procedures and accommodations to ensure that SSC occurs as a safe and positive experience for the parent, family, infant, and health care team. This statement includes all families as defined and determined by themselves, and recognizes that health communication, language, and terminology must be individualized to meet specific family needs by the health care team.
Phylogenetic Profiling Analysis of the Phycobilisome Revealed a Novel State-Transition Regulator Gene in Synechocystis sp. PCC 6803
Authors: Fukunaga Tsukasa , Ogawa Takako , Iwasaki Wataru , Sonoike Kintake
Published: July 2024

Phycobilisomes play a crucial role in the light-harvesting mechanisms of cyanobacteria, red algae and glaucophytes, but the molecular mechanism of their regulation is largely unknown. In the cyanobacterium, Synechocystis sp. PCC 6803, we identified slr0244 as a phycobilisome-related gene using phylogenetic profiling analysis, a method used to predict gene function based on comparative genomics. To investigate the physiological function of the slr0244 gene, we characterized slr0244 mutants spectroscopically. Disruption of the slr0244 gene impaired state transition, a process by which the distribution of light energy absorbed by the phycobilisomes between two photosystems is regulated in response to the changes in light conditions. The Slr0244 protein seems to act in the process of state transition, somewhere at or downstream of the sensing step of the redox state of the plastoquinone (PQ) pool. These findings, together with past reports describing the interaction of this gene product with thioredoxin and glutaredoxin, suggest that the slr0244 gene is a novel state-transition regulator that integrates the redox signal of PQ pools with that of the photosystem I-reducing side. The protein has two universal stress protein (USP) motifs in tandem. The second motif has two conserved cysteine residues found in USPs of other cyanobacteria and land plants. These redox-type USPs with conserved cysteines may function as redox regulators in various photosynthetic organisms. Our study also shows the efficacy of phylogenetic profiling analysis in predicting the function of cyanobacterial genes that have not been annotated so far.
Lighting the way: Compelling open questions in photosynthesis research
Authors: Eckardt Nancy A , Allahverdiyeva Yagut , Alvarez Clarisa E , Büchel Claudia , Burlacot Adrien , Cardona Tanai , Chaloner Emma , Engel Benjamin D , Grossman Arthur R , Harris Dvir , Herrmann Nicolas , Hodges Michael , Kern Jan , Kim Tom Dongmin , Maurino Veronica G , Mullineaux Conrad W , Mustila Henna , Nikkanen Lauri , Schlau-Cohen Gabriela , Tronconi Marcos A , Wietrzynski Wojciech , Yachandra Vittal K , Yano Junko
Published: July 2024

Photosynthesis—the conversion of energy from sunlight into chemical energy—is essential for life on Earth. Yet there is much we do not understand about photosynthetic energy conversion on a fundamental level: how it evolved and the extent of its diversity, its dynamics, and all the components and connections involved in its regulation. In this commentary, researchers working on fundamental aspects of photosynthesis including the light-dependent reactions, photorespiration, and C4 photosynthetic metabolism pose and discuss what they view as the most compelling open questions in their areas of research.
The transcription factors ZAT5 and BLH2/4 regulate homogalacturonan demethylesterification in Arabidopsis seed coat mucilage
Authors: Xie Minmin , Ding Anming , Guo Yongfeng , Sun Jinhao , Qiu Wanya , Chen Mingli , Li Zhiyuan , Li Shanshan , Zhou Gongke , Xu Yan , Wang Meng , Richel Aurore , Gong Daping , Kong Yingzhen
Published: July 2024

The level of methylesterification alters the functional properties of pectin, which is believed to influence plant growth and development. However, the mechanisms that regulate demethylesterification remain largely unexplored. Pectin with a high degree of methylesterification is produced in the Golgi apparatus and then transferred to the primary cell wall where it is partially demethylesterified by pectin methylesterases (PMEs). Here, we show that in Arabidopsis (Arabidopsis thaliana) seed mucilage, pectin demethylesterification is negatively regulated by the transcription factor ZINC FINGER FAMILY PROTEIN5 (ZAT5). Plants carrying null mutations in ZAT5 had increased PME activity, decreased pectin methylesterification, and produced seeds with a thinner mucilage layer. We provide evidence that ZAT5 binds to a TGATCA motif and thereby negatively regulates methylesterification by reducing the expression of PME5, HIGHLY METHYL ESTERIFIED SEEDS (HMS)/PME6, PME12, and PME16. We also demonstrate that ZAT5 physically interacts with BEL1-LIKE HOMEODOMAIN2 (BLH2) and BLH4 transcription factors. BLH2 and BLH4 are known to modulate pectin demethylesterification by directly regulating PME58 expression. The ZAT5–BLH2/4 interaction provides a mechanism to control the degree of pectin methylesterification in seed coat mucilage by modifying each transcription factor's ability to regulate the expression of target genes encoding PMEs. Taken together, these findings reveal a transcriptional regulatory module comprising ZAT5, BLH2, and BLH4, that functions in modulating the demethylesterification of homogalacturonan in seed coat mucilage.
Debt and taxes: the role of corporate group structure
Authors: Brok Peter
Published: July 2024

I show that the corporate group structure generates tax benefits that create incentives for higher leverage. The tax benefits arise when losses on distressed subsidiaries are tax deductible for a parent firm. Higher tax rates then imply that more of these losses are borne by the government instead of the parent firm, reducing the expected costs of bankruptcy and thereby incentivizing the subsidiaries to take on higher leverage. Using data from a large sample of European multinationals, I show that this tax benefit exists on top of the trade-off theory and debt-shifting effects, and is stronger when deductions of subsidiary losses are more generous.
Why right-wing governments restrict market competition: a demographic theory
Authors: Huo Jingjing
Published: July 2024

Recent scholarship on the evolution of neoliberalism points out that, despite free market discourse, right-wing rule has often resulted in re-regulation and further market concentration, to the advantage of large corporations. This article argues that such an outcome is not an inevitable result of right-wing incumbency. Instead, I identify an exogenous, demographic, change that prompts right-wing governments to increasingly embrace market concentration: the aging of the workforce, which has intensified the substitution of capital for labor, and as a result, somewhat paradoxically, reduced the amount of pure profits that can be distributed to wealthy households. In response, right-wing governments restrict competition to shore up pure profits. Drawing on data from 14 to 20 OECD countries, I show that as workforce aging intensifies, right partisanship becomes increasingly associated with more regulatory restrictions on competition, greater market concentration, and a greater pure profit share of income.
Surveilling Sureties: How Privately Mediated Monetary Sanctions Enroll and Responsibilize Families
Authors: Deckard Faith M
Published: July 2024

In the neoliberal age, ordinary people are increasingly responsible for taking up crime control and surveillance, what we might consider traditional state functions. This article situates commercial bail as a case of responsibilization and identifies monetary sanctions as a mechanism through which private companies offload pretrial risk management onto families. Drawing on ethnographic and interview data, I present this process via four stages. First, agents use cosigned bail bonds to selectively enroll people they perceive as suitable sureties and surveillants. Second, this monetary sanction is deployed with carceral and financial threats to encourage cosigners to embody the roles. Third, as surveillants, family members engage in invisible emotional labor to cope with or rationalize their deployment as an arm of the state. Last, through their involvement as instruments of surveillance, family members inadvertently become subjects of surveillance and carceral control. From enrollment to subjugation, this process of responsibilization is an uneven one as women, particularly women of color, are disproportionately burdened with risk management and any resulting repercussions.
Exploring the Intention to Engage in Policy Practice: The Role of Values and Career Motivations
Authors: Krips Oron , Tartakovsky Eugene , Weiss-Gal Idit
Published: July 2024

This study expands knowledge on what motivates engagement in policy practice (PP) by exploring the place of personal values, which reflect individuals’ general motivations and context-specific motivations—the motivations to study social work—in predicting the intention to incorporate PP into their practice. The sample of this cross-sectional study comprised 280 BSW students in Israel, and the study employed the Portrait Values Questionnaire–Refined, Social Work Career Influence Questionnaire, and the PP Intention Scale. Path analysis showed that personal values were associated with PP intention both directly and indirectly through the motivations to study social work. However, the mechanisms differ for self-transcendence versus self-enhancement and openness to change versus conservation values. A stronger PP intention was associated with a higher preference for openness to change versus conservation values mediated by the social change motivation to study social work. The total effect of the preference for self-enhancement versus self-transcendence values on PP intention was nonsignificant. This resulted from the contradiction between the negative direct and positive indirect effects (through the social change motivation) of these values on PP intention. The study results underscore the place of personal values and motivations to study social work in explaining PP intention.
Sesaminol alters phospholipid metabolism and alleviates obesity‐induced NAFLD
Authors: Rajendran Rajprabu , Suman Sanskriti , Divakaran Soumya Jaya , Swatikrishna Sahu , Tripathi Purnima , Jain Rashi , Sagar Karan , Rajakumari Sona
Published: July 2024

The prevalence of obesity‐induced non‐alcoholic fatty liver disease (NAFLD) and insulin resistance is increasing worldwide. We previously demonstrated that sesaminol increases thermogenesis in adipocytes, improves insulin sensitivity, and mitigates obesity in mice. In this study, we demonstrated that sesaminol increased mitochondrial activity and reduced ROS production in hepatocytes. Therefore, we delve into the metabolic action of sesaminol in obesity‐induced NAFLD or metabolic dysfunction‐associated liver disease (MAFLD). Here, we report that sesaminol induces OXPHOS proteins and mitochondrial function in vivo. Further, our data suggest that sesaminol administration reduces hepatic triacylglycerol accumulation and LDL‐C levels. Prominently, the lipidomics analyses revealed that sesaminol administration decreased the major phospholipids such as PC, PE, PI, CL, and PS to maintain membrane lipid homeostasis in the liver upon HFD challenge. Besides, SML reduced ePC and SM molecular species and increased PA levels in the HFD‐fed mice. Also, sesaminol renders anti‐inflammatory properties and dampens fibrosis markers in the liver. Remarkably, SML lowers the hepatic levels of ALT and AST enzymes and alleviates NAFLD in diet‐induced obese mice. The molecular docking analysis identifies peroxisome proliferator‐activated receptors as potential endogenous receptors for sesaminol. Together, our study demonstrates plant lignan sesaminol as a potential small molecule that alters the molecular species of major phospholipids, including sphingomyelin and ether‐linked PCs in the liver tissue, improves metabolic parameters, and alleviates obesity‐induced fatty liver disease in mice.
Interplay of miRNAs and molecular pathways in spaceflight‐induced depression: Insights from a rat model using simulated complex space environment
Authors: Rasheed Madiha , Tahir Rana Adnan , Maazouzi Mohamed , Wang Han , Li Yumeng , Chen Zixuan , Deng Yulin
Published: July 2024

Depression is a significant concern among astronauts, yet the molecular mechanisms underlying spaceflight‐induced depression remain poorly understood. MicroRNAs (miRNAs) have emerged as potential regulators of neuropsychiatric disorders, including depression, but their specific role in space‐induced depression remains unexplored. This study aimed to elucidate the involvement of candidate miRNAs (miR‐455‐3p, miR‐206‐3p, miR‐132‐3p, miR‐16‐5p, miR‐124‐3p, and miR‐145‐3p) and their interaction with differentially expressed genes (DEGs) in the neurobiology of spaceflight‐induced depressive behavior. Using a simulated space environmental model (SCSE) for 21 days, depressive behavior was induced in rats, and candidate miRNA expressions and DEGs in the cortex region were analyzed through qRT‐PCR and HPLC, respectively. Results showed that SCSE‐exposed rats exhibited depressive behaviors, including anhedonia, increased immobility, and anxiousness compared to controls. Further analysis revealed increased hydrogen peroxide levels and decreased superoxide dismutase levels in the SCSE group, indicating abnormal oxidative stress in the cerebral cortex. Moreover, miRNA analysis demonstrated significant upregulation of miR‐455‐3p, miR‐206‐3p, miR‐132‐3p, and miR‐16‐5p expression. Among the DEGs identified, the in silico analysis highlighted their involvement in crucial pathways such as glutamatergic signaling, GABA synaptic pathway, and calcium signaling, implicating their role in spaceflight‐induced depression. Protein–protein interaction analysis identified hub genes, including DLG4, DLG3, GRIN1, GRIN2B, GRIN2A, SYNGAP1, DLGAP1, GRIK2, and GRIN3A, impacting neuronal dysfunction functions in the cortex region of SCSE depressive rats. DLG4 emerged as a core gene regulated by miR‐455‐3p and miR‐206‐3p. Overall, this study underscores the potential of miRNAs as biomarkers for mood disorders and neurological abnormalities associated with spaceflight, advancing health sciences, and space health care.
Molecular mechanism of bitter taste receptor agonist‐mediated relaxation of airway smooth muscle
Authors: Conaway Stanley , Huang Weiliang , Hernandez‐Lara Miguel A. , Kane Maureen A. , Penn Raymond B. , Deshpande Deepak A.
Published: July 2024

G‐protein‐coupled receptors (GPCRs) belonging to the type 2 taste receptors (TAS2Rs) family are predominantly present in taste cells to allow the perception of bitter‐tasting compounds. TAS2Rs have also been shown to be expressed in human airway smooth muscle (ASM), and TAS2R agonists relax ASM cells and bronchodilate airways despite elevating intracellular calcium. This calcium “paradox” (calcium mediates contraction by pro‐contractile Gq‐coupled GPCRs) and the mechanisms by which TAS2R agonists relax ASM remain poorly understood. To gain insight into pro‐relaxant mechanisms effected by TAS2Rs, we employed an unbiased phosphoproteomic approach involving dual‐mass spectrometry to determine differences in the phosphorylation of contractile‐related proteins in ASM following the stimulation of cells with TAS2R agonists, histamine (an agonist of the Gq‐coupled H1 histamine receptor) or isoproterenol (an agonist of the Gs‐coupled β2‐adrenoceptor) alone or in combination. Our study identified differential phosphorylation of proteins regulating contraction, including A‐kinase anchoring protein (AKAP)2, AKAP12, and RhoA guanine nucleotide exchange factor (ARHGEF)12. Subsequent signaling analyses revealed RhoA and the T853 residue on myosin light chain phosphatase (MYPT)1 as points of mechanistic divergence between TAS2R and Gs‐coupled GPCR pathways. Unlike Gs‐coupled receptor signaling, which inhibits histamine‐induced myosin light chain (MLC)20 phosphorylation via protein kinase A (PKA)‐dependent inhibition of intracellular calcium mobilization, HSP20 and ERK1/2 activity, TAS2Rs are shown to inhibit histamine‐induced pMLC20 via inhibition of RhoA activity and MYPT1 phosphorylation at the T853 residue. These findings provide insight into the TAS2R signaling in ASM by defining a distinct signaling mechanism modulating inhibition of pMLC20 to relax contracted ASM.
SPP1 could be an immunological and prognostic biomarker: From pan‐cancer comprehensive analysis to osteosarcoma validation
Authors: Zhang Zhiming , Liu Binfeng , Lin Zhengjun , Mei Lin , Chen Ruiqi , Li Zhihong
Published: July 2024

Secreted phosphoprotein 1 (SPP1), also known as osteopontin, is a phosphorylated protein. High SPP1 expression levels have been detected in multiple cancers and are associated with poor prognosis and reduced survival rates. However, only a few pan‐cancer analyses have targeted SPP1. We conducted a comprehensive analysis using multiple public databases, including TIMER and TCGA, to investigate the expression levels of SPP1 in 33 different tumor types. In addition, we verified the effect of SPP1 on osteosarcoma. To assess the impact of SPP1 on patient outcomes, we employed univariate Cox regression and Kaplan–Meier survival analyses to analyze overall survival (OS), disease‐specific survival (DSS), and progression‐free interval (PFI) in these tumor patients. We also explored SPP1 gene alterations in various tumor tissues using cBioPortal. We then examined the relationship between SPP1 and clinical characteristics, TME, immune regulatory genes, immune checkpoints, TMB, and MSI using R language. In addition, we used GSEA to investigate the molecular mechanisms underlying the role of SPP1. Bioinformatics analysis indicated that SPP1 was upregulated in 17 tumors. Overexpression of SPP1 results in poor OS, DSS, and PFI in CESC, ESCA, GBM, LGG, LIHC, PAAD, PRAD, and skin cutaneous melanoma. SPP1 expression was positively associated with immunocyte infiltration, immune regulatory genes, immune checkpoints, TMB, MSI, and drug sensitivity in certain cancers. We found that high expression of SPP1 in osteosarcoma was related to drug resistance and metastasis and further demonstrated that SPP1 can stimulate osteosarcoma cell proliferation via CCND1 by activating the PI3K/Akt pathway. These findings strongly suggest that SPP1 is a potential prognostic marker and novel target for cancer immunotherapy.
Enhancing Transition to Nursing Practice: The Mental Health Immersion Experience
Authors: Peters Anita L. , Weber Lisa A. , Cichra Nancy , Goliat Laura
Published: July 2024

The number of people facing mental health issues continues to grow in the aftermath of COVID-19. Nurses are challenged with providing care for an increasing number of patients, including veterans, with complex mental health needs across healthcare settings. Of concern, many students transitioning into practice feel they lack the necessary confidence, education, and skills to competently care for patients with mental health illness. This article discusses an innovative mental health immersion experience strategically integrated within a new-nurse residency program.
Effect of Remimazolam on Transcranial Electrical Motor-evoked Potential in Spine Surgery: A Prospective, Preliminary, Dose-escalation Study
Authors: Kurita Shuichiro , Furutani Kenta , Mitsuma Yusuke , Deguchi Hiroyuki , Kamoda Tomoaki , Kamiya Yoshinori , Baba Hiroshi
Published: July 2024

Background:

Some anesthetic drugs reduce the amplitude of transcranial electrical motor-evoked potentials (MEPs). Remimazolam, a new benzodiazepine, has been suggested to have little effect on MEP amplitude. This prospective, preliminary, dose-escalation study aimed to assess whether remimazolam is associated with lower MEP amplitude in a dose-dependent manner.

Methods:

Ten adult patients scheduled for posterior spinal fusion were included in this study. General anesthesia was induced with a continuous infusion of remifentanil and remimazolam. After the patient lost consciousness, the infusion rate of remimazolam was set to 1 mg/kg/h, and the patient underwent tracheal intubation. Baseline MEPs were recorded under 1 mg/kg/h of remimazolam in a prone position. Thereafter, the infusion rate of remimazolam was increased to 2 mg/kg/h, with a bolus of 0.1 mg/kg. Ten minutes after the increment, the evoked potentials were then recorded again. The primary endpoint was the MEP amplitude recorded in the left gastrocnemius muscle at 2 time points.

Results:

There was no difference in MEP amplitude recorded from the left gastrocnemius muscle before and after increasing remimazolam (median [interquartile range]: 0.93 [0.65 to 1.25] mV and 0.70 [0.43 to 1.26] mV, respectively;P=0.08). The average time from the cessation of remimazolam administration to neurological examination after surgery was 4 minutes using flumazenil.

Conclusions:

This preliminary study suggests that increasing remimazolam from 1 to 2 mg/kg/h might have an insignificant effect on transcranial electric MEPs.
In utero exposure to antihistamines and risk of hepatocellular carcinoma in a multigenerational cohort
Authors: Murphy Caitlin C. , Seif El Dahan Karim , Singal Amit G. , Cirillo Piera M. , Krigbaum Nickilou Y. , Cohn Barbara A.
Published: July 2024

Background:

Growing evidence suggests that liver disease originates in early life. Antihistamines cross the placenta and are frequently prescribed to pregnant women to treat nausea and vomiting, as well as allergy and asthma symptoms. Exposure to antihistamines in utero may impact the developing liver by reprogramming or inducing epigenetic changes in fetal hepatocytes.

Methods:

We examined in utero exposure to antihistamines and the risk of HCC in the Child Health and Development Studies, a multigenerational cohort that enrolled pregnant women in the East Bay, CA, between 1959 and 1966 (n=14,507 mothers and 18,751 liveborn offspring). We reviewed mothers’ medical records to identify those prescribed antihistamines during pregnancy, and diagnoses of HCC in adult (age ≥18 y) offspring were identified by linkage with a population-based cancer registry. Cox proportional hazard models were used to estimate adjusted hazard ratios, with follow-up accrued from birth through cancer diagnosis, death, or last contact.

Results:

About 15% of offspring (n=2759 of 18,751) were exposed in utero to antihistamines. Chlorpheniramine (51.8%) and diphenhydramine (15.4%) were the 2 most commonly prescribed antihistamines. Any in utero exposure was not associated with HCC (adjusted hazard ratio: 2.76, 95% CI: 0.70, 10.89), but the association differed by timing of exposure. Offspring exposed to antihistamines in the first or second trimester had a higher risk of HCC compared to offspring not exposed (adjusted hazard ratio: 4.64, 95% CI: 1.21, 17.78). Similarly, incidence rates were 4.3 per 100,000 (95% CI: 0.9, 12.6) for offspring exposed in the first or second trimester compared to 1.0 per 100,000 (95% CI: 0.3, 2.1) for offspring not exposed.

Conclusions:

In utero exposure to antihistamines in early pregnancy may increase the risk of HCC in adulthood.
A Partner-Engaged Approach to Developing an Implementation Research Logic Model for a Traumatic Brain Injury-Intensive Evaluation and Treatment Program
Authors: Haun Jolie N. , Melillo Christine , Schneider Tali , McDaniel Justin , McMahon-Grenz Julie , Benzinger Rachel C. , Nakase-Richardson Risa , Pugh Mary Jo V. , Skop Karen M. , Friedman Yvonne , Sandoval Roberto , Sabangan Jerome , Samson Kimberly , Picon Linda M. , Kean Jacob
Published: July 2024

Background:

A partnered evaluation project with Veterans Health Administration Physical Medicine and Rehabilitation program office uses a partner-engaged approach to characterize and evaluate the national implementation of traumatic brain injury (TBI)Intensive Evaluation and Treatment Program (IETP).

Objective:

This paper illustrates a partner-engaged approach to contextualizing the IETP within an implementation research logic model (IRLM) to inform program sustainment and spread.

Setting:

The project was conducted at five IETP sites: Tampa, Richmond, San Antonio, Palo Alto, and Minneapolis.

Participants:

Partners included national and site program leaders, clinicians, Department of Defense Referral Representatives, and researchers. Participants included program staff (n = 46) and Service Members/Veterans (n = 48).

Design:

This paper represents a component of a larger participatory-based concurrent mixed methods quality improvement project.

Main Measures:

Participant scripts and demographic surveys.

Methods:

Datasets were analyzed using rapid iterative content analysis; IETP model was iteratively revised with partner feedback. Each site had an IETP clinical team member participate. The IRLM was contextualized within the Consolidated Framework for Implementation Research (CFIR); systematic consensus building expert reviewed implementation strategies; RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance); and Implementation Outcomes Framework (IOF).

Results:

Analyses and partner feedback identified key characteristics, determinants, implementation strategies, mechanisms, and outcomes.

Conclusions:

This partner-engaged IRLM informs implementation and sustainment of a rehabilitation program for individuals with TBI. Findings will be leveraged to examine implementation, standardize core outcome measurements, and inform knowledge translation.
Normothermic regional perfusion in controlled DCD liver procurement: Outcomes of the Swedish national implementation protocol
Authors: Bluhme Emil , Gäbel Markus , Martinez de la Maza Lilia , Nilsén Vera , Hildebrand Karin , Jarsäter Jenni , Bååth Cecilia , Proos Matilda , Romano Antonio , Villard Christina , Oniscu Gabriel C. , Gustafsson Niklas , Thompson Monica , Hansson Christoffer , Löfstedt Margareta , Andersson Lindholm Jonas , Falk Lars , Bennet William , Jorns Carl
Published: July 2024

Liver transplantation (LTX) using donors after controlled circulatory death (cDCD) is associated with poorer graft survival and increased incidence of nonanastomotic biliary strictures (NASs) compared to livers procured from brain-dead donors (DBD). The use of normothermic regional perfusion (NRP) during cDCD procurement may improve posttransplant outcomes and reduce the incidence of NAS. In Sweden, cDCD LTX was introduced through a national pilot protocol with mandatory NRP. This study aims to evaluate the outcome of cDCD LTX during the pilot period. Donor and recipient data were collected on all cDCD liver transplants during the pilot period between January 2020 to December 2022. Outcome on NAS, patient and graft survival, early allograft dysfunction, acute kidney injury, and comprehensive complication index was compared to a matched cohort of 28 patients transplanted with a DBD liver between 2018 and 2022. Eighteen patients were transplanted with a liver from a cDCD donor after using NRP. The mean functional warm ischemia time was 29 ± 6 minutes. The mean lactate reduction during NRP was 8.7 ± 2.4 mmol/L, and the end NRP perfusate alanine aminotransferase was 1.4 ± 1 µkat/L. When comparing recipients of cDCD liver transplant to DBD, no significant differences were observed in the incidence of NAS, patient and graft survival, comprehensive complication index, early allograft dysfunction, or acute kidney injury. Study protocol magnetic resonance cholangiopancreatography in cDCD patients showed no signs of subclinical biliary strictures. Evaluation of the Swedish national pilot of cDCD LTX with mandatory NRP shows comparable outcomes to a matched DBD cohort with 94.4% 1-year patient and graft survival and no incidence of NAS within the first year.
Clinical Outcomes Among High-Risk Primary Care Patients With Diabetic Kidney Disease
Authors: Bosworth Hayden B. , Patel Uptal D. , Lewinski Allison A. , Davenport Clemontina A. , Pendergast Jane , Oakes Megan , Crowley Matthew J. , Zullig Leah L. , Patel Sejal , Moaddeb Jivan , Miller Julie , Malone Shauna , Barnhart Huiman , Diamantidis Clarissa J.
Published: July 2024

Background/Objective:

Slowing the progression of diabetic kidney disease (DKD) is critical. We conducted a randomized controlled trial to target risk factors for DKD progression.

Methods:

We evaluated the effect of a pharmacist-led intervention focused on supporting healthy behaviors, medication management, and self-monitoring on decline in estimated glomerular filtration rate (eGFR) for 36 months compared with an educational control.

Results:

We randomized 138 individuals to the intervention group and 143 to control. At baseline, mean (SD) eGFR was 80.7 (21.7) mL/min/1.73m2, 56% of participants had chronic kidney disease and a history of uncontrolled hypertension with a baseline SBP of 134.3 mm Hg. The mean (SD) decline in eGFR by cystatin C from baseline to 36 months was 5.0 (19.6) and 5.9 (18.6) mL/min/1.73m2 for the control and intervention groups, respectively, with no significant between-group difference (P=0.75).

Conclusions:

We did not observe a significant difference in clinical outcomes by study arm. However, we showed that individuals with DKD will engage in a pharmacist-led intervention. The potential explanations for a lack of change in DKD risk factors can be attributed to 5 broad issues, challenges: (1) associated with enrolling patients with low eGFR and poor BP control; (2) implementing the intervention; (3) limited duration during which to observe any clinical benefit from the intervention; (4) potential co-intervention or contamination; and (5) low statistical power.
Predictors of Health-Related Quality of Life in Younger Persons With a Fecal Ostomy and Inflammatory Bowel Disease
Authors: Werther Caitlin
Published: July 2024

PURPOSE:

The purpose of this study was to determine predictors of health-related quality of life (HRQOL) in persons aged 18 to 40 years living with inflammatory bowel disease (IBD) and a fecal ostomy.

DESIGN:

Descriptive cross-sectional study.

SUBJECTS AND SETTING:

The sample comprised 98 participants recruited from online discussion boards/support groups for individuals living with IBD and an intestinal ostomy. More than three-quarters (76.5%) were female; 45.9% (n = 44) had lived with an ostomy for 2 years or less. Data were collected through an online survey made available from October 2018 to December 2018.

METHODS:

HRQOL was measured using the Healthy Days Core Module (Centers for Disease Control and Prevention HRQOL-4). Item 1 from the CDC HRQOL-4 represented the variable self-rated health (SRH). The subscales of bodily pain, general mental health, and vitality from the Short-Form 36 Health Survey and the subscales of ostomy function and body image/sexuality plus skin irritation item from the Young-Fadok Stoma Quality of Life (QOL) Scale were used to measure predictors of pain, psychological distress, fatigue, peristomal skin irritation, leakage of ostomy appliance, and body image/sexual disturbance. Correlational and hierarchical multiple linear regression analyses were conducted to complete hypotheses testing.

RESULTS:

Significant correlations were found between pain, fatigue, peristomal skin problems, psychological distress, SRH, and HRQOL. Pain, fatigue, psychological distress, and self-related health explained 53.2% of the variance in HRQOL based on hierarchical multiple linear regression and controlling for demographic variables such as marital and employment status.

CONCLUSIONS:

Findings suggest global disease symptoms of IBD in the form of pain, fatigue, and psychological distress and individual perception of health (SRH) are more important than transient ostomy symptoms of peristomal skin complications and leakage of ostomy appliance in predicting HRQOL. Individuals in this population regularly use online resources indicating a need to understand and gain insight into the information posted online in the management of the fecal ostomy and IBD.
The Correlation Between Comfort Level and Quality of Life in Female Patients With Urinary Incontinence
Authors: Gülnar Emel , Yuvanç Ercan , Çalışkan Nurcan
Published: July 2024

PURPOSE:

The aim of this study was to develop a model to determine the correlation between comfort level and quality of life in women with UI.

DESIGN:

Cross-sectional, descriptive correlational research design with causal modeling.

SUBJECTS AND SETTING:

The study was conducted in the urology outpatient clinic of a university hospital in the Central Anatolia region of Turkey. The sample comprised 233 women admitted to the outpatient clinic between December 2017 and May 2018. Participants had a mean age of 52.5 (SD = 13.9) years.

METHODS:

Data were collected using a researcher-designed Descriptive Characteristics Form, the Incontinence Quality of Life (I-QOL) form, the Urinary Incontinence and Frequency Comfort Questionnaire (UIFCQ), and the Short Form-36 (SF-36). Multivariate correlations were analyzed using structural equation modeling; an AMOS covariance-based structural equation model was developed.

RESULTS:

The correlational pathway between I-QOL, UIFCQ, and SF-36 was statistically significant. As a result of the confirmed model, I-QOL scores were moderately correlated with SF-36 scores (r = .65, P = .001) and highly correlated with UIFCQ scores (r = .76, P = .001). Mean UIFCQ scores were moderately correlated with SF-36 scores (r = .66, P = .001). The structural equation modeling resulted in a model with a good fit.

CONCLUSIONS:

The higher the comfort level, the higher the UI-specific and health-related quality of life. Risk factors related to UI should be monitored, and necessary training and counseling should be provided to eliminate this common problem.
Spatial food webs in the Barents Sea: atlantification and the reorganization of the trophic structure
Authors: Jordán Ferenc , Capelli Greta , Primicerio Raul , Hidas András , Fábián Virág , Patonai Katalin , Bodini Antonio
Published: July 2024

Climate change affects ecosystems at several levels: by altering the spatial distribution of individual species, by locally rewiring interspecific interactions, and by reorganizing trophic networks at larger scales. The dynamics of marine food webs are becoming more and more sensitive to spatial processes and connections in the seascape. As a case study, we study the atlantification of the Barents Sea: we compare spatio-temporal subsystems at three levels: the identity of key organisms, critically important interactions and the entire food web. Network analysis offers quantitative measurements, including centrality indices, trophic similarity indices, a topological measure of interaction asymmetry and network-level measures. We found that atlantification alters the identity of key species (boreal demersals becoming hubs), results in strongly asymmetric interactions (dominated by haddock), changes the dominant regulation regime (from bottom-up to wasp-waist control) and makes the food web less modular. Since the results of food web analysis may be quite sensitive to network construction, the aggregation of food web data was explicitly studied to increase the robustness of food web analysis. We found that an alternative, mathematical aggregation algorithm better preserves some network properties (e.g. density) of the original, unaggregated network than the biologically inspired aggregation into functional groups.

This article is part of the theme issue ‘Connected interactions: enriching food web research by spatial and social interactions’.
Erosion of fish trophic position: an indirect effect of fishing on food webs elucidated by stable isotopes
Authors: Agnetta Davide , Badalamenti Fabio , Sweeting Christopher J. , D'Anna Giovanni , Libralato Simone , Pipitone Carlo
Published: July 2024

Fishing has significant trophodynamic impacts on marine communities, including reductions in the mean trophic position (TP) of the ecosystem resulting from a decrease in the abundance and size of species and individuals with high TPs. This study demonstrates the erosion of fish TP, an additional process that results in lower TP of individuals of a given size, which may exacerbate the effects of fishing on the food web. A stable isotope approach based on the tRophicPosition Bayesian method was used to quantify the TP of 12 target marine species at a given length, and compare their TP between fishery-restricted areas and trawled areas. The results show a difference in the TP of six benthic and apical nekto-benthic predators, which feed in the median at about 0.5 TP lower in trawled areas. It appears that current ‘fishing down marine food webs’ analyses may underestimate the trophic effects of fishing. Accounting for changes in trophodynamics of individuals at a given size is important to detect indirect effects through food web interactions. The application of a trawling ban may lead to the restoration of lost trophic structure; however, trophic changes may occur more slowly than changes in biomass.

This article is part of the theme issue ‘Connected interactions: enriching food web research by spatial and social interactions’.