bluuebunny/crossref_metadata_2025 huggingface dataset:
Tumor cell-intrinsic SETD2 inactivation sensitizes cancer cells to immune checkpoint blockade through the NR2F1-STAT1 pathway
Authors: Zheng Xufen , Luo Yuxiang , Xiong Yangjie , Liu Xiaoxiao , Zeng Chunling , Lu Xiaojing , Wang Xiaofang , Cheng Yumei , Wang Simin , Lan Haoqi , Wang Kai , Weng Zhonghui , Bi Wenbo , Gan Xinxin , Jia Xiaona , Wang Linhui , Wang Yuexiang
Published: December 2023

Background

Cancer immunotherapies can induce durable tumor regression, but most patients do not respond.SETD2mutation has been linked to the efficacy of immune checkpoint inhibitors (ICIs) immunotherapy. The functional importance of the SETD2 inactivation and how to modulate immunotherapy response remains unclear.

Methods

To explore the function of SETD2 in immunotherapy, knockout and subsequent functional experiments were conducted. Bulk RNA-seq, ATAC-seq, Chip-seq and single-cell RNA-seq were performed to dissect the mechanism and explore the immune microenvironment of mouse tumor. Flow cytometry was used to assess cell surface antigen and intratumoral T cell levels.

Results

We comprehensively determine the effect of SETD2 inactivation in ICIs therapy and elucidate the mechanistic impact on tumor immunity. Murine syngeneic tumors harboringSetd2inactivation are sensitive to ICIs. By bulk and single-cell RNA-seq, we further reveal that SETD2 inactivation reprograms intratumoral immune cells and inflames the tumor microenvironment, which is characterized by high infiltration of T cells and enhanced antigen presentation to activate CD8+T cell-mediated killing. Mechanistically, via an integrated multiomics analysis using ATAC-seq, ChIP-seq and RNA-seq, we demonstrate that SETD2 inactivation reducesNR2F1transcription by impairing H3K36me3 deposition and chromatin accessibility, which activates the STAT1 signaling pathway to promote chemokines and programmed cell death protein-1 (PD-1) expression and enhance antigen presentation. All these regulatory mechanisms synergistically promote the effects of anti-programmed cell death ligand 1 immunotherapy inSetd2-knockout syngeneic mouse models. The SETD2-NR2F1-STAT1 regulatory axis is conserved in human and murine cancers. Finally, cancer patients harboringSETD2mutations who received ICIs show increased durable clinical benefits and survival.

Conclusions

These findings provide novel insights into the biology of SETD2 inactivation regulation and reveal a new potential therapeutic biomarker for ICIs immunotherapy in various refractory cancers.
A Conflict-Resilient Lock-Free Linearizable Calendar Queue
Authors: Marotta Romolo , Ianni Mauro , Pellegrini Alessandro , Quaglia Francesco
Published: December 2023

In the last two decades, great attention has been devoted to the design of non-blocking and linearizable data structures, which enable exploiting the scaled-up degree of parallelism in off-the-shelf shared-memory multi-core machines. In this context, priority queues are highly challenging. Indeed, concurrent attempts to extract the highest-priority item are prone to create detrimental thread conflicts that lead to abort/retry of the operations. In this article, we present the first priority queue that jointly provides: (i) lock-freedom and linearizability; (ii) conflict resiliency against concurrent extractions; (iii) adaptiveness to different contention profiles; and (iv) amortized constant-time access for both insertions and extractions. Beyond presenting our solution, we also provide proof of its correctness based on an assertional approach. Also, we present an experimental study on a 64-CPU machine, showing that our proposal provides performance improvements over state-of-the-art non-blocking priority queues.
How Should an AI Trust its Human Teammates? Exploring Possible Cues of Artificial Trust
Authors: Jorge Carolina Centeio , Jonker Catholijn M. , Tielman Myrthe L.
Published: December 2023

In teams composed of humans, we use trust in others to make decisions, such as what to do next, who to help and who to ask for help. When a team member is artificial, they should also be able to assess whether a human teammate is trustworthy for a certain task. We see trustworthiness as the combination of (1) whether someone will do a task and (2) whether they can do it. With building beliefs in trustworthiness as an ultimate goal, we explore which internal factors (krypta) of the human may play a role (e.g., ability, benevolence, and integrity) in determining trustworthiness, according to existing literature. Furthermore, we investigate which observable metrics (manifesta) an agent may take into account as cues for the human teammate’s krypta in an online 2D grid-world experiment (
n
= 54). Results suggest that cues of ability, benevolence and integrity influence trustworthiness. However, we observed that trustworthiness is mainly influenced by human’s playing strategy and cost-benefit analysis, which deserves further investigation. This is a first step towards building informed beliefs of human trustworthiness in human-AI teamwork.
Democratic Norms and the Ethics of Resistance
Authors: Chapman Emilee Booth
Published: December 2023

Most democratic theories recognize that democracy requires widespread adherence to both formal and informal norms that constrain the use of power and structure relationships among citizens. Most also recognize that a healthy democracy requires some forms of activism or resistance that transgress those norms to disrupt hierarchies, challenge injustices, and drive discursive innovation. Recent systemic theories of democracy show that democratic theory can incorporate these two realities without contradiction, but it is not clear whether an ethic of citizenship can do the same. This article reviews recent literature on the purposes and ethics of transgressive politics while also drawing attention to neglected questions about the functions of democratic norms and how they are maintained amid transgressions. These are questions that must be addressed by an ethic of citizenship that can navigate the tension between the authority of democratic norms and the constructive potential of transgressive politics.
Fatigue Life Analysis of Remanufactured Radial Rolling Bearing with the Replaced Loading Zone
Authors: Chen L. , Bu D. T. , Feng Z. B. , Liu H. B.
Published: December 2023

The replacement of the loading zone is not considered in the active calculation method on fatigue life of remanufactured bearings. In practical application, when the radial bearings are reinstalled after remanufacturing, it is required to replace the loading zone, which results in a large deviation between the calculated fatigue life according to the active calculation method and the actual life. In this paper, the fatigue life factors of radial bearings with different remanufacturing levels are calculated according to the actual application condition. The results of case studies show that with the improvement of the remanufacturing level, regardless of whether the loading zone is replaced or not, the remanufacturing bearing life factor is gradually increased and the maximum can reach 1. Considering the replacement of the loading zone, the life factors of remanufactured bearings with different fixed rings are also very different, among which the remanufacturing deviation of fixed outer-ring level II is the largest, reaching 11.3%. However, with the increase of the remanufacturing level, the deviation decreases gradually. The life factors by the method presented in this paper of remanufactured radial bearings with the replaced loading zone are significantly higher than those of the active calculation method. The research results of this paper provides a more accurate calculation scheme for the fatigue life of remanufactured radial rolling bearings, which is a supplement to the active calculation method and has important practical significance for the practice of bearing remanufacturing engineering.
Improved Finite Difference Technique via Adomian Polynomial to Solve the Coupled Drinfeld’s–Sokolov–Wilson System
Authors: Younis Israa Th. , Al-Rawi Ekhlass S.
Published: December 2023

This study presents a new algorithm for effectively solving the nonlinear coupled Drinfeld’s–Sokolov–Wilson (DSW) system using a hybrid explicit finite difference technique with the Adomian polynomial (EFD‐AP). The suggested approach addresses the problem of accurately solving the DSW system. Numerical results are obtained by comparing the exact solution with absolute and mean square errors using a test problem to assess the EFD‐AP accuracy against the exact solution and the conventional explicit finite difference (EFD) method. The results exhibit excellent agreement between the approximate and exact solutions at different time values, and the results showed that the proposed EFD‐AP method achieves superior accuracy and efficiency compared to the EFD method, which makes it a promising method for solving nonlinear partial differential systems of higher order.
Quality of Life and Social Inclusion of Migrants and Refugees Attending an Elderly Care Training in Four Mediterranean Countries: Results from the HERO Project
Authors: Santini Sara , Finco Matteo , Fabbietti Paolo , Moza Sotiria , Kyprianou Elena , Yerou Christina , Tsitsi Theologia , Soulé Maria Victoria , Charalambous Andreas , Kassidakis Panos , Galassi Flavia
Published: December 2023

The progressive population ageing observed in Western countries determines a growing need for long-term care for older people. At the same time, migrants and refugees often have integration difficulties in regards to the hosting country society and labour market, with one reason being the lack of EU recognition of the educational degrees obtained in their native country. Creating educational opportunities in elderly care for migrants may facilitate their social inclusion, increase their employability, and constitute a response to the growing labor demand. The HERO project moved in this direction by planning, designing, and carrying out an original training curriculum targeted to migrants and refugees from African and Middle Eastern countries, piloted in four Mediterranean countries (Cyprus, Greece, Italy, and Portugal). The impact of the training on migrants and refugees’ quality of life was assessed through the WHOQOL-BREF questionnaire, while social inclusion was assessed through semistructured interviews and participant observation carried out during the internship in elderly care facilities. Eighty-two migrants (70.7 percent women) were involved in the study. The results showed that despite the fact that the training did not have an impact on the trainees’ quality of life, it was associated with social inclusion. Four ideal types of migrant learners were drawn: “ex-professional trainees,” “fall-back trainees,” “care-oriented trainees,” and “nonprofessional care workers,” based on which as many possible educational pathways were drawn to optimise the trainees’ learning process. The study results shaped the formulation of suggestions on migrants’ education in elderly care.
Role of Gut Microbiota, Immune Imbalance, and Allostatic Load in the Occurrence and Development of Diabetic Kidney Disease
Authors: Han Yi Zhen , Zheng Hui Juan , Du Bo Xuan , Zhang Yi , Zhu Xing Yu , Li Jing , Wang Yao Xian , Liu Wei Jing
Published: December 2023

Diabetic kidney disease (DKD) is a prevailing complication arising from diabetes mellitus. Unfortunately, there are no trustworthy and efficacious treatment modalities currently available. In recent times, compelling evidence has emerged regarding the intricate correlation between the kidney and the gut microbiota, which is considered the largest immune organ within the human physique. Various investigations have demonstrated that the perturbation of the gut microbiota and its associated metabolites potentially underlie the etiology and progression of DKD. This phenomenon may transpire through perturbation of both the innate and the adaptive immunity, leading to a burdensome allostatic load on the body and ultimately culminating in the development of DKD. Within this literature review, we aim to delve into the intricate interplay between the gut microbiota, its metabolites, and the immune system in the context of DKD. Furthermore, we strive to explore and elucidate potential chemical interventions that could hold promise for the treatment of DKD, thereby offering invaluable insights and directions for future research endeavors.
Myeloid Cells Pave the Metastatic Road in Breast Cancer
Authors: Michaud Daniel E. , Guerriero Jennifer L.
Published: December 2023

Current immunotherapeutic approaches are tailored towards biomarkers and mechanisms presented in the primary tumor microenvironment, yet few are designed against targets that arise in the metastatic site. In a recent Cancer Discovery article, Yofe and colleagues spatially and temporally mapped the evolving breast tumor metastatic environment within the lung at single-cell resolution to identify immunologic cell types and mechanisms underlying the formation of metastatic nodules. The authors identified myeloid cell, monocyte, and neutrophil phenotypes as the most significant differences between the primary tumor and metastatic site. The authors also revealed the existence of a metastasis-specific population of macrophages expressing Trem2 in both human and murine models that exhibit immunosuppressive features. Interestingly, Trem2+ macrophages are enriched at the invasive border of metastatic nodules compared with the metastatic core, suggesting they play an exclusionary role within the site. Characterization of the premetastatic lung in conjunction with pseudotime lineage analysis revealed that Fn1+ monocytes precede metastasis formation and are the likely source of Trem2+ macrophages in developed nodules. This study supports the characterization of metastatic immune microenvironments to identify novel immunotherapeutic targets that may not exist within the primary site but play a significant role in patient outcome.
Combined Inhibition of EZH2 and FGFR is Synergistic in BAP1-deficient Malignant Mesothelioma
Authors: Badhai Jitendra , Landman Nick , Pandey Gaurav Kumar , Song Ji-Ying , Hulsman Danielle , Krijgsman Oscar , Chandrasekaran Gayathri , Berns Anton , van Lohuizen Maarten
Published: December 2023

Malignant mesothelioma is a highly aggressive tumor with a survival of only 4–18 months after diagnosis. Treatment options for this disease are limited. Immune checkpoint blockade using ipilimumab and nivolumab has recently been approved as a frontline therapy, but this led to only a small improvement in overall patient survival. As more than half of patients with mesothelioma have alterations in the gene encoding for BAP1 this could be a potential marker for targeted therapies. In this study, we investigated the synergistic potential of combining EZH2 inhibition together with FGFR inhibition for treatment of BAP1-deficient malignancies. The efficacy of the combination was evaluated using human and murine preclinical models of mesothelioma and uveal melanoma in vitro. The efficacy of the combination was further validated in vivo by using BAP1-deficient mesothelioma xenografts and autochthonous mouse models. In vitro data showed sensitivity to the combined inhibition in BAP1-deficient mesothelioma and uveal melanoma tumor cell lines but not for BAP1-proficient subtypes. In vivo data showed susceptibility to the combination of BAP1-deficient xenografts and demonstrated an increase of survival in autochthonous models of mesothelioma. These results highlight the potential of this novel drug combination for the treatment of mesothelioma using BAP1 as a biomarker. Given these encouraging preclinical results, it will be important to clinically explore dual EZH2/FGFR inhibition in patients with BAP1-deficient malignant mesothelioma and justify further exploration in other BAP1 loss–associated tumors.

Significance:

Despite the recent approval of immunotherapy, malignant mesothelioma has limited treatment options and poor prognosis. Here, we observe that EZH2 inhibitors dramatically enhance the efficacy of FGFR inhibition, sensitising BAP1-mutant mesothelioma and uveal melanoma cells. The striking synergy of EZH2 and FGFR inhibition supports clinical investigations for BAP1-mutant tumors.
Comparing Protein and Gene Expression Signature between Nasal Polyps and Nasal Fluids in Chronic Rhinosinusitis
Authors: Hou Yilin , Chen Changhui , Li Zhengqi , Lu Tong , Sun Lin , Wei Yi , Li Jian , Wen Weiping
Published: December 2023

Introduction: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a serious inflammatory condition. Nasal fluids (NFs) present a noninvasive alternative to nasal biopsy for studying CRSwNP pathogenesis. We aimed to compare the protein and mRNA inflammation signature between nasal polyps (NPs) and NFs. Method: The performance of polyvinyl alcohol (PVA) sponges and NFs absorbable device (NFAD) for collecting NFs from 20 patients with CRSwNP was compared using the Luminex assay. The other group consisted of four healthy controls and an additional 21 CRSwNP patients (including eosinophilic CRSwNP [ECRSwNP] and non-eosinophilic CRSwNP [NECRSwNP]) for protein quantification by Olink platform and gene expression evaluation by RNA-sequencing. Spearman’s analysis was performed to detect correlations between protein expression levels in NFs and clinical assessment variables. Results: NFAD-collected NFs contained at least a 2-fold higher concentration of cytokines than that obtained using PVA sponge, and these cytokines levels are significantly associated with NPs (ρ > 0.45, p < 0.05). Differentially expressed proteins between NFs and NPs were significantly correlated in the ECRSwNP subgroup compared with controls (ρ = 0.41, p < 0.01). Levels of Th2/IL-13, MCP4, and CCL4, characteristic of eosinophilic infiltration, were increased in ECRSwNP patients. A significant correlation between gene and protein expression was observed (ρ = 0.34, p < 0.01). PDL2 levels in NFs were positively correlated with ECRSwNP postoperative recurrence, the nasal VAS, and SNOT-22 scores (ρ > 0.68, p < 0.05 for all). Conclusion: Our study revealed similarities and discrepancies in inflammatory signatures between NPs and NFs in the same CRSwNP patient.
Differentially Expressed miR-511-3p in Stroke Patients Predicts the Presence of Post-Stroke Cognitive Impairment
Authors: Wang Te , Zhao Wei , Liu Yan , Song Kangping , Zeng Junsheng , Wang Zhen
Published: December 2023

Introduction: Stroke is common cerebrovascular disease in the elderly, which is characterized by neurological defects caused by cerebral vessels. Multiple studies have shown that miRNAs play important roles in stroke. In addition, a large number of evidence suggest that stroke increases the risk and severity of cognitive impairments. Methods: miR-511-3p expression levels were detected by real-time PCR. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic value of miR-511-3p in distinguishing stroke patients from healthy controls and to assess risk of post-stroke cognitive impairment (PSCI) in stroke patients. Pearson correlation coefficient was used to determine the relationship between miR-511-3p expression level and Montreal Cognitive Assessment Scale (MoCA) scores. Results: Serum miR-511-3p expression levels were decreased in stroke patients, and the decrease was more significant in PSCI patients. ROC curve results showed that miR-511-3p had high diagnostic accuracy in distinguishing healthy controls from stroke patients. Moreover, the expression level of miR-511-3p can be used as an independent predictor for the occurrence of PSCI and is positively correlated with MoCA scores of PSCI patients. Conclusion: miR-511-3p may be involved in the occurrence and development of stroke. In addition, miR-511-3p may be a novel biomarker for predicting PSCI occurred in stroke patients. These results may help improve the quality of prognosis of stroke.
CHALLENGES FOR GREEN INFRASTRUCTURE FROM THE PERSPECTIVE OF BRAZILIAN RESEARCHERS
Authors: Sant'Anna Camila Gomes , Hannes Evy , Sakata Francine Gramacho
Published: December 2023

The topic of Green Infrastructure (GI) has been debated with growing interest in Brazil as a tool to achieve more resilient cities, specially in terms of urban drainage and water supply. In Brazilian universities, the discussion was brought by professors influenced by the ideas of Ian McHarg expressed in his iconic work Design with Nature, which has recently had a new impulse after the publication of the studies from Mark Benedict and Edward McMahon. In 2019 there was a certain amount of Brazilian researches on the field of GI, but it is still difficult to apply and develop GI concepts in a tropical weather and with economically poor conditions. This article aims to bring advances and challenges GI studies are facing now in Brazil, from the perspective of the workshop entitled Rethinking the Green City, held in April 2019 in Brasilia, which promoted the meeting of 36 British and Brazilian researchers. The topics highlighted from the presentations and discussions from the workshop were: the weakness of the State to plan and provide solutions for water pollution, drainage and urban forms; the lack of awareness in general on the importance to incorporate the natural processes on planning strategies; and the need for strategies to change patterns (and thoughts) to incorporate GI concepts. Researchers have to figure out how to present GI in these conditions in the time to come.
Arte ornamental em jardins de cura infantis
Authors: Passos Luciana Andrade dos , Souza Tricia Jully Lemos Pravitz de , Medeiros Joshua Matheus Silva Lucena de
Published: December 2023

Os ornamentos também integram espaços de jardins de cura. No entanto, é essencial que os objetos artísticos comuniquem mensagens apropriadas para estímulos à cura interior. Nesse sentido, o objetivo deste artigo é compreender a leitura visual dos ornamentos de jardins de cura infantis. Particularmente, este estudo tem o interesse de revelar o potencial de identificabilidade dos ornamentos, sob o enfoque dos materiais, das silhuetas, das linhas de contornos e dos padrões de informação de objetos expostos nos jardins. A análise da linguagem visual dos objetos de cinco jardins de cura infantis, construídos entre 1999 e 2018 nos Estados Unidos, permitiu interpretar que os ornamentos também podem exibir silhuetas não identificáveis ou expressar fatores visuais negativos. Tal alerta pode ser útil para orientar a concepção de ornamentos de jardins destinados ao público específico de pacientes infantis com deficiências ou em processo de reabilitação.
Comparison of Stress-Rest and Stress-LGE Analysis Strategy in Patients Undergoing Stress Perfusion Cardiovascular Magnetic Resonance
Authors: Swoboda Peter P. , Matthews Gareth D.K. , Garg Pankaj , Plein Sven , Greenwood John P.
Published: December 2023

BACKGROUND:

Stress perfusion cardiovascular magnetic resonance can be performed without rest perfusion for the quantification of ischemia burden. However, the optimal method of analysis is uncertain.

METHODS:

We identified 666 patients from CE-MARC (Clinical Evaluation of Magnetic Resonance Imaging in Coronary Heart Disease) with complete stress perfusion, rest perfusion, late gadolinium enhancement (LGE), and quantitative coronary angiography data. For each segment of the 16-segment model, perfusion was visually graded during stress and rest imaging, with infarct transmurality assessed from LGE imaging. In the stress-LGE analysis, a segment was defined as ischemic if it had a subendocardial perfusion defect with no infarction. Rest perfusion was not used in this analysis. We compared the diagnostic accuracy of stress-LGE analysis against quantitative coronary angiography and the stress-rest method validated in the original CE-MARC analysis. The diagnostic accuracy of the stress-LGE method was evaluated with different thresholds of infarct transmurality used to define whether an infarcted segment had peri-infarct ischemia.

RESULTS:

The optimal stress-LGE analysis classified all segments with a stress perfusion defect as ischemic unless they had >75% infarct transmurality (area under the curve, 0.843; sensitivity, 75.6%; specificity, 93.1%;
P
<0.001). This analysis method has superior diagnostic accuracy to the stress-rest method (area under the curve, 0.834; sensitivity, 73.6%; specificity, 93.1%;
P
<0.001,
P
value for difference=0.02). Patients were followed-up for median 6.5 years for major adverse cardiovascular events, with the presence of inducible ischemia by either the stress-LGE or stress-rest analysis being similar and strongly predictive (hazard ratio, 2.65;
P
<0.001, for both).

CONCLUSIONS:

In this analysis of CE-MARC, the optimum definition of inducible ischemia was the presence of a stress-induced perfusion defect without transmural infarction. This definition improved the diagnostic accuracy compared with the stress-rest analysis validated in the original study. The absence of ischemia by either analysis strategy conferred a favorable long-term prognosis.
Publicly Engaged Sociological Research for Immigrant Well-Being
Authors: Menjívar Cecilia
Published: December 2023

Drawing inspiration from the long tradition of U.S. sociology and from Latin American sociology, I describe a few examples of how I have endeavored to make my scholarship available to the public and to inform policy to enhance immigrant well-being. I frame this piece within discussions around public, policy, critical, and professional sociology to underscore that these strands of the discipline do not conflict but draw strength from one another. Identifying urgent issues that need our research attention is key to doing this work effectively to contribute to social change.
Can we do our scholarship with our backs to Auschwitz? Gregory Baum, evil and the public role of the religious studies scholar
Authors: Seljak David
Published: December 2023

In his 1987 book Compassion and Solidarity, Gregory Baum recounts a story told by the German Roman Catholic theologian and priest Johann Baptist Metz, who, in response to the Holocaust, developed a guiding principle: ‘You cannot do theology with your back turned to Auschwitz’. Baum challenges scholars to ask the same question. What is the cost of doing scholarship with one’s back turned to Auschwitz and other forms of radical evil? Does not business-as-usual scholarship risk conforming to the dominant culture and practices of our time, no matter what? Does it not risk pushing scholars to acquiesce to the neo-liberal model of the depoliticized, neutralized scholar? Baum’s refusal to ‘do scholarship’ with his back to evil highlights the necessity and urgency of using scholarly expertise to participate in public debates. First, society needs the unique expertise of scholars of religion to address its many interconnected crises. Second, participation in public debates affords scholars the opportunity to develop a self-critical spirit and to look for signs of ideological taint and distorting messages in their work. Participating in public debates results in better scholarship, Baum argues, but only if one adopts a critical-humanistic approach rooted in an emancipatory commitment, a hermeneutics of suspicion, and the perspective of the victims, the marginalized and the excluded. In other words, socially engaged scholarship is only valid when it is critical – as well as self-critical – scholarship. Baum’s approach promotes a scholarly humility about truth claims that avoids inauthentic universalisms. David Seljak explores the necessity and urgency of participation in public debates by the religious studies scholar by examining Baum’s biography, public role and its impact on his scholarship.
Is Sacubitril/Valsartan a Superior Agent in Heart Failure With Reduced Ejection Fraction? A Review of Randomized Comparative Trials
Authors: Rindone Joseph P. , Mellen Chadwick K. , Goldenstein Megan
Published: December 2023

Background: The PARADIGM HF trial showed sacubitril/valsartan (SV) to be superior to enalapril in patients with reduced ejection fraction (HFrEF). Since its publication, several other randomized trials have compared SV to either an angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) in HFrEF which showed conflicting results regarding mortality, hospitalizations, and quality of life scoring. Objective: To review randomized comparative trials of SV to either ACEI or ARB in patients with HFrEF. Methods: PubMed and Embase databases were used to identify randomized comparative trials. The text terms sacubitril, angiotensin neprilysin, and LCZ696 were used for both searches. Meta-analysis, retrospective, adhoc, and cohort studies were excluded. Results: 1476 and 3983 citations were reviewed on PubMed and Embase, respectively. Of these, 11 randomized comparative trials to either ACEI or ARB were included for analysis. The mortality/quality of life benefits of SV over enalapril in the PARADIGM HF were not corroborated in any of the other trials. The effect of hospitalizations for heart failure was inconsistent among trials. Exercise tolerance was not improved with SV versus enalapril. Conclusion: The results of the PARADIGM HF trial have largely not been confirmed in subsequent randomized comparative trials.
Empowering Nursing Students to Prevent Medication Error-Related Harms: A Step Toward Improving Patient Safety
Authors: Deswal Himani , Mittal Niti , Kaushal Jyoti , Kumar Sumit , Kaushik Pankaj
Published: December 2023

Aim: Existing gaps in nursing curriculum particularly related to medication management such as administration and monitoring increase the propensity of nurses to commit medication errors during clinical practice. The present training program was conducted with an aim to sensitize and educate undergraduate nursing students on medication errors’ related aspects. Methods: The participants were students pursuing bachelors nursing degree course (second and third year). The training “Medication errors: Role of Nurse practitioners” comprised of blended teaching methods such as theme lectures, hands on training exercises, small group case‑based learning, role plays, and nursing officer’s practical experiences. The participants’ knowledge and perception about medication errors were assessed at baseline (pre-intervention phase) and 1 week after program (post-intervention phase) with the help of a structured self-administered questionnaire in English language. Results: A total of 110 nursing students participated in the program. Post program there was a consistent increase in the number of correct responses to all knowledge-based questions with a significant improvement in knowledge scores from baseline [Baseline: (mean ± SD) 12.62 ± 2.33; Post-training: 18.52 ± 2.22; P < .001]. There was a positive change in the perception about medication errors among students. The participants rated the overall quality of program as excellent [66 (60%)] or very good [40 (36.4%)]. More than 90% agreed on its applicability in their future practice. Conclusions: The training was quite successful in educating nursing students on medication errors. There is a constant need to educate nurses and other healthcare providers including doctors and pharmacists on medication safety related aspects with an ultimate goal to improve patient safety.
Benefits of Accepting Infectious Diseases Pharmacist Recommendations: A 5-Year Outcome Study in a Multihospital System
Authors: Babiarz Taylor , Schmetterer Justin , Merrick Kelley , Jelic Tanja , Roberts Thomas
Published: December 2023

Background: Infectious diseases (ID) pharmacists are pivotal members of antimicrobial stewardship teams. Prospective audit and feedback is a strong recommendation by The Infectious Diseases Society of America Guidelines for Antimicrobial Stewardship Programs (ASP). Utilizing customized ASP intervention documentation tools known as “ivents” in Epic, we aimed to assess the impact of interventions by measuring outcomes that were accepted compared to those that were rejected in a multihospital health system over 5 years. Methods: A multicenter, retrospective cohort study was conducted to compare clinical outcomes among intensive care unit (ICU) and non-ICU patients with accepted and rejected ASP interventions over 5 years from October 2015 to December 2020. Outcomes measured included antibiotic days of therapy per 1000 patient days (DOT/1000 PD), antibiotic doses per 1000 patient days (doses/1000 PD), hospital length of stay (LOS), in-hospital mortality, hospital-acquired Clostridioides difficile infection (HA-CDI), community-onset C. difficile infection (CO-CDI) within 30 days, and hospital readmission within 30 days. Coarsened exact matching (CEM) was used as a non-parametric matching method to balance covariates between groups and to control for confounding. Results: ASP recommendations by ID pharmacists were well-received by providers in a multihospital system over 5 years as evidenced by an overall acceptance rate of 92%. Acceptance of ASP interventions was associated with substantial reductions in antibiotic utilization without adversely affecting mortality or hospital readmissions. While high-risk C. difficile antibiotic use increased significantly due to frequent de-escalation to ceftriaxone among non-ICU patients with accepted interventions, rates of HA-CDI and CO-CDI within 30 days did not worsen. Furthermore, hospital LOS was notably shorter by an average of 1 day for non-ICU patients with accepted interventions, which resulted in substantial cost avoidance of $7 631 400. Conclusion: Collaboration with ID pharmacists to optimize antimicrobial stewardship was associated with significant reductions in antibiotic utilization, costs, and hospital LOS without worsening patient outcomes.
Prevalence and correlates of psychological distress among national community-based adult populations in Nauru, Tukelau and Tuvalu
Authors: Pengpid Supa , Peltzer Karl
Published: December 2023

Aims:

The aim of the study was to estimate the prevalence and correlates of psychological distress (PD) in three small Pacific Island countries.

Method:

National cross-sectional data (pooled sample N = 3,088, 18–69 years) of participants from the STEPS surveys in Nauru (2015/16; N = 1382), Tukelau (2014; N = 554) and Tuvalu (2015; N = 1152) were analysed.

Results:

In the pooled sample 30.4% participants had PD (⩾20 scores), 18.1% mild (20–24 scores), 7.8% moderate (25–29 scores) and 4.4% severe (30–50 scores) PD. The prevalence of PD in Nauru was 41.5%, in Tukelau 5.0% and in Tuvalu 22.7%. In the adjusted logistic regression analysis with the pooled sample, younger age (18–39 years), alcohol family problems, heart attack/stroke, current smoking, high salt intake and high sedentary behaviour were positively associated with PD, while male sex and being from Tukelau and Tuvalu were negatively associated with PD.

Conclusion:

Almost one in three participants reported PD and several associated factors were found that can be targeted in population interventions.
Front Is High and Back Is Low: Sound-Space Iconicity in Finnish
Authors: Vainio Lari , Kilpeläinen Markku , Wikström Alexandra , Vainio Martti
Published: December 2023

Previous investigations have shown various interactions between spatial concepts and speech sounds. For instance, the front-high vowel [i] is associated with the concept of forward, and the back-high vowel [o] is associated with the concept of backward. Three experiments investigated whether the concepts of forward/front and backward/back are associated with high- and low-pitched vocalizations, respectively, in Finnish. In Experiments 1 and 2, the participants associated the high-pitched vocalization with the forward-directed movement and the low-pitched vocalizations with the backward-directed movement. In Experiment 3, the same effect was observed in relation to the concepts of front of and back of. We propose that these observations present a novel sound-space symbolism phenomenon in which spatial concepts of forward/front and backward/back are iconically associated with high- and low-pitched speech sounds. This observation is discussed in relation to the grounding of semantic knowledge of these spatial concepts in the movements of articulators such as relative front/back-directed movements of the tongue.
A systematic practice review: Providing palliative care for people with Parkinson’s disease and their caregivers
Authors: Garon Michela , Weck Christiane , Rosqvist Kristina , Odin Per , Schrag Anette , Krikmann Ülle , Pedrosa David J , Antonini Angelo , Lorenzl Stefan , Martins Pereira Sandra , Paal Piret
Published: December 2023

Background:

People with Parkinson’s disease has significant and increasing physical, psychosocial and spiritual needs, as well as problems with coordination and continuity of care. Despite the benefits that palliative care could offer, there is no consensus on how it should be delivered.

Aim:

The aim of this study is to provide a pragmatic overview of the evidence to make clinical recommendations to improve palliative care for people with Parkinson’s disease and their caregivers.

Design:

A systematic review method was adopted to determine the strength of evidence, supported by feedback from an expert panel, to generate the ‘do’, ‘do not do’ and ‘do not know’ recommendations for palliative care.

Data sources:

Searches were conducted via OVID to access CINAHL, MEDLINE, EMBASE and the Cochrane Library from 01/01/2006 to 31/05/2021. An additional search was conducted in December 2022. The search was limited to articles that included empirical studies of approaches to enabling palliative care.

Results:

A total of 62 studies met inclusion criteria. There is evidence that education about palliative care and movement disorders is essential. palliative care should be multi-disciplinary, individualised and coordinated. Proactive involvement and support of caregivers throughout the illness is recommended. Limited data provide referral indicators for palliative care integration. Discussions about advance care planning should be held early.

Conclusions:

Consideration of palliative care integration based on symptom burden and personal preferences, coordination and continuity of care are needed to maintain the quality of life of people with Parkinson’s disease and their caregivers.
Parents’ experiences of being involved in medical decision-making for their child with a life-limiting condition: A systematic review with narrative synthesis
Authors: Polakova Kristyna , Ahmed Faraz , Vlckova Karolina , Brearley Sarah G
Published: December 2023

Background:

Parental involvement in the decision-making processes about medical treatment for children with life-limiting conditions is recognised as good practice. Previous research highlighted factors affecting the decision-making process, but little is known about how parents experience their participation.

Aim:

To explore how parents experience their participation in the process of decision-making about treatment and future care for their children with life-limiting conditions.

Design:

A systematically constructed review using narrative synthesis. The PRISMA guidelines were followed to report the findings. Databases Medline, EMBASE, SCOPUS, CINAHL and PsycINFO were searched up to December 2023. The study protocol was registered at PROSPERO (RN CRD42021215863).

Results:

From the initial 2512 citations identified, 28 papers met the inclusion criteria and were included in the review. A wide range of medical decisions was identified; stopping general or life-sustaining treatment was most frequent. Narrative synthesis revealed six themes: (1) Temporal aspects affecting the experience with decision-making; (2) Losing control of the situation; (3) Transferring the power to decide to doctors; (4) To be a ‘good’ parent and protect the child; (5) The emotional state of parents and (6) Sources of support to alleviate the parental experience.

Conclusions:

Parental experiences with decision-making are complex and multifactorial. Parents’ ability to effectively participate in the process is limited, as they are not empowered to do so and the circumstances in which the decisions are taking place are challenging. Healthcare professionals need to support parental involvement in an effective way instead of just formally asking them to participate.
When small effect sizes become huge: Synaesthesia is linked to very large differences in cognition
Authors: Ward Jamie
Published: December 2023

The replication crisis has taught us to expect small-to-medium effects in psychological research. But this is based on effect sizes calculated over single variables. Mahalanobis D, the multivariate equivalent of Cohen's d, can enable very large group differences to emerge from a collection of small-to-medium effects (here, reanalysing multivariate datasets from synaesthetes and controls). The use of multivariate effect sizes is not a slight of hand but may instead be a truer reflection of the degree of psychological differences between people that has been largely underappreciated.
Inter-institutional analysis of the outcome after postcardiotomy veno-arterial extracorporeal membrane oxygenation
Authors: Biancari Fausto , Mäkikallio Timo , Loforte Antonio , Kaserer Alexander , Ruggieri Vito G , Cho Sung-Min , Kang Jin Kook , Dalén Magnus , Welp Henryk , Jónsson Kristján , Ragnarsson Sigurdur , Hernández Pérez Francisco J , Gatti Giuseppe , Alkhamees Khalid , Fiore Antonio , Lechiancole Andrea , Rosato Stefano , Spadaccio Cristiano , Pettinari Matteo , Perrotti Andrea , Sahli Sebastian D , L’Acqua Camilla , Arafat Amr A , Albabtain Monirah A , AlBarak Mohammed M , Laimoud Mohamed , Djordjevic Ilija , Krasivskyi Ihor , Samalavicius Robertas , Jankuviene Agne , Alonso-Fernandez-Gatta Marta , Wilhelm Markus J , Juvonen Tatu , Mariscalco Giovanni
Published: December 2023

Introduction:

Patients requiring postcardiotomy veno-arterial extracorporeal membrane oxygenation (V-A-ECMO) have a high risk of early mortality. In this analysis, we evaluated whether any interinstitutional difference exists in the results of postcardiotomy V-A-ECMO.

Methods:

Studies on postcardiotomy V-A-ECMO were identified through a systematic review for individual patient data (IPD) meta-analysis. Analysis of interinstitutional results was performed using direct standardization, estimation of observed/expected in-hospital mortality ratio and propensity score matching.

Results:

Systematic review of the literature yielded 31 studies. Data from 10 studies on 1269 patients treated at 25 hospitals were available for the present analysis. In-hospital mortality was 66.7%. The relative risk of in-hospital mortality was significantly higher in six hospitals. Observed versus expected in-hospital mortality ratio showed that four hospitals were outliers with significantly increased mortality rates, and one hospital had significantly lower in-hospital mortality rate. Participating hospitals were classified as underperforming and overperforming hospitals if their observed/expected in-hospital mortality was higher or lower than 1.0, respectively. Among 395 propensity score matched pairs, the overperforming hospitals had significantly lower in-hospital mortality (60.3% vs 71.4%, p = 0.001) than underperforming hospitals. Low annual volume of postcardiotomy V-A-ECMO tended to be predictive of poor outcome only when adjusted for patients’ risk profile.

Conclusions:

In-hospital mortality after postcardiotomy V-A-ECMO differed significantly between participating hospitals. These findings suggest that in many centers there is room for improvement of the results of postcardiotomy V-A-ECMO.
Development and evaluation of a risk score model based on a WNT score gene-associated signature for predicting the clinical outcome and the tumour microenvironment of hepatocellular carcinoma
Authors: Li Penghui , Ma Xiao , Huang Di , Gu Xinyu
Published: December 2023

Background: Hepatocellular carcinoma (HCC) is currently one of the most life-threatening diseases worldwide. However, the factors, genes, and processes involved in the mechanisms of HCC initiation, development, and metastasis remain to be identified.

Methods: WNT signalling pathways may play important roles in cancer initiation and progression. Thus, it would be informative to construct a WNT signature-based gene model for the prognosis of HCC and the prediction of therapeutic efficacy. We curated genomic profiles for HCC from The Cancer Genome Atlas (TCGA) and divided them into training and internal validation datasets. We also used samples from GSE14520 and HCCDB18 as validation datasets and clustered them by ConsensusClusterPlus analysis. We applied WebGestaltR to the WNT score-associated differentially expressed genes (DEGs) and conducted a signalling pathway enrichment analysis. We assessed the tumour immune microenvironment with ESTIMATE, Microenvironment Cell Populations (MCP)-counter, single-sample gene set enrichment analysis (ssGSEA), and tumour immune dysfunction and exclusion (TIDE).

Results: We performed a least absolute shrinkage and selection operator (LASSO) regression analysis to identify the prognosis-related hub genes, identified the risk and protective factor genes associated with HCC, classified them into two clusters, and found that Cluster 2 had a significantly better prognosis than Cluster 1. Moreover, the latter had advanced clinical features compared with the former. Uridine-cytosine kinase 1 (UCK1), myristoylated alanine-rich C-kinase substrate-like protein 1 (MARCKSL1), P-antigen family member 1 (PAGE1), and killer cell lectin-like receptor B1 (KLRB1) were detected and used to construct a simplified prognostic model for HCC. The high risk score subgroup showed a poorer prognosis than the low risk score subgroup, and the model assessed HCC prognosis consistently and effectively.

Conclusions: The WNT score-related gene-based model designed and evaluated herein had strong prognostic and predictive ability for HCC and could, therefore, facilitate decision-making in the prognosis and therapeutic efficacy assessment of HCC.
How leader's type shapes the effect of nuclear latency on dispute involvement
Authors: Jones Benjamin , Mattiacci Eleonora , Nordstrom Timothy
Published: December 2023

What is the effect of nuclear latency on states’ conflict behaviors? Defined as the ability to produce fissile material without the actual possession of nuclear weapons, nuclear latency is much more common in the international system than nuclear weapons are. Yet present studies might have underestimated its impact on conflict. We argue that, given its ambiguous nature as a dual-use technology, nuclear latency has the potential to significantly alter the effect of leader type on conflict. In particular, while conventional wisdom about hawks and doves suggests that the former should be more prone to conflict than the latter, nuclear latency blurs the distinction between leader's types. Bridging together studies of nuclear latency and leader type, we study how nuclear latency shapes the impact of leader type on the propensity of initiating conflict or being targeted. We find that in the absence of latency, hawkish leaders are more likely to initiate disputes than dovish leaders. However, latency muddies the waters. Thus, leader characteristics does not affect dispute initiation for latent states.
Theory-Based Nursing Policy to Enhance Living Quality: A Book Review of Policy & Politics in Nursing and Health Care (8th ed.) by Mason and colleagues (2021). Elsevier.
Authors: Doe Mi Jin
Published: December 2023

In this article, the author presents a review of the 8th edition of Policy & Politics in Nursing and Health Care edited by Mason and colleagues (2021). The book provides comprehensive insights into policy and politics in nursing and healthcare with a foundation of extensive practical information, highlighting the significance of nursing leadership. It prompted the author to reflect on the crucial role of nursing knowledge in shaping nursing policy, and to explore nursing leadership and policies through the distinct lens of the humanbecoming leading-following model.