bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of AI ethics awareness, attitude, anxiety, and self-efficacy on nursing students’ behavioral intentions
Authors: Kwak Yeunhee , Ahn Jung-Won , Seo Yon Hee
Published: September 2022

Background

Artificial intelligence (AI) technology has recently seen rapid advancement, with an expanding role and scope in nursing education and healthcare. This study identifies the influence of AI ethics awareness, attitude toward AI, anxiety, and self-efficacy on nursing students’ behavioral intentions to use AI-based healthcare technology.

Methods

The participants included 189 nursing students in Gyeonggi-do, with data collected from November to December 2021 using self-reported questionnaires. We analyzed the data using the SPSS/WIN 26.0 program, including a t-test, Pearson’s correlation coefficient, and hierarchical multiple linear regression.

Results

The results revealed that AI ethical awareness (t = − 4.32, p < .001), positive attitude toward AI (t = − 2.60, p = .010), and self-efficacy (t = − 2.65, p = .009) scores of the third and fourth-year nursing students were higher, while their anxiety scores were lower (t = 2.30, p = .022) compared to the scores of the first and second-year nursing students. The factors influencing behavioral intention included a positive attitude toward AI (β = 0.58) and self-efficacy (β = 0.22). The adjusted R2 was 0.42.

Conclusion

It is necessary to inculcate a positive attitude toward AI and self-efficacy by providing educational programs on AI-based technology in healthcare settings.
Explaining specific taxes management and use in the health sector: a qualitative study
Authors: Kooshkebaghi Mahdi , Emamgholipour Sara , Dargahi Hossein
Published: September 2022

Background and aim

Being the major source of revenue and essential economic tool for policymakers to improve public health, taxes contribute to government spending on the development of health care facilities and services. Given the financial challenges facing the health sector together with the public health issues that affect each society, placing specific taxes on some goods, services, and activities can be effective in this regard. The study aims to explain the various dimensions of specific taxes in the health sector and management of these resources in order to achieve the health system goals.

Materials and methods

This study with a qualitative research design was conducted using semi-structured interviews with open-ended questions in 2020–2021. In total, 38 managers, policymakers, economists, key experts, and other individuals, as informants, were interviewed. Purposive and snowball with maximum variation was also employed. As well, content analysis was utilized to shed light on the data. The transcribed interviews were further imported into MAXQDA for extracting and classifying the relevant codes.

Findings

In this study, 5 main themes and 23 subthemes were labeled. The main themes accordingly included “Objectives and Conditions of Specific Health Taxes”, “Earmarked Taxes”, “Taxes on Goods and Measures of Harmful to Health”, “Value-Added Taxes”, and “Green Taxes”.

Discussion and conclusion

Considering the specific taxes in the health sector, i.e., taxes on goods and measures of harmful to health, value-added taxes, and green taxes, all taxation and pricing policies need to take account of the effects as well as the advantages and disadvantages of types of taxes, a country’s economic structure, the conditions of industries and manufacturing enterprises, cultural aspects in society, and peoples’ socioeconomic status.
Incorporating ‘reason for use’ into the prescribing process of medication: a survey on the opinion of patients in Flanders, Belgium
Authors: Peeters Marijke , Iturrospe Elias , Jans Dominique , van Nuijs Alexander L. N. , De Loof Hans
Published: September 2022

Background

A longstanding debate exists about including a ‘reason for use’ on prescriptions for medication. Little is known, however, about patients’ opinions on this subject.

Methods

An internet-based questionnaire, consisting mainly of Likert scale questions, was distributed online to the general public in Belgium. Results from 1034 responses were analyzed using descriptive statistics.

Results

Opinions from patients toward including a ‘reason for use’ on medication prescriptions were generally positive. A clear majority of 62% increased to 74% after providing information about the possible link between indication and medication dose. A majority of the participants expressed a positive attitude regardless of the pathology involved, although sexually transmitted diseases were of greatest concern. Other important aspects differentiating the opinion positively was the transmission of this information in an electronic-only form and limiting it to the regular pharmacist excluding further use by third parties such as other pharmacies or insurance companies. Patients using multiple medicines and those frequenting the same pharmacy also had a more favorable opinion about including the reason for use. In addition, analysis of physician and pharmacist questionnaire responses, explicitly excluded from the main analysis, confirmed the known contrasting opinions in these subgroups.

Conclusions

Patients have strong support for transferring information on the ‘reason for use’ of their prescriptions to their regular pharmacy if this is done in a secure and privacy-conscious way enabling increased patient safety and improved pharmaceutical care.
Mutagenesis of the odorant receptor co-receptor (Orco) reveals severe olfactory defects in the crop pest moth Helicoverpa armigera
Authors: Fan Xiao-Bin , Mo Bao-Tong , Li Guo-Cheng , Huang Ling-Qiao , Guo Hao , Gong Xin-Lin , Wang Chen-Zhu
Published: September 2022

Background

Odorant receptors (ORs) as odorant-gated ion channels play a crucial role in insect olfaction. They are formed by a heteromultimeric complex of the odorant receptor co-receptor (Orco) and a ligand-selective Or. Other types of olfactory receptor proteins, such as ionotropic receptors (IRs) and some gustatory receptors (GRs), are also involved in the olfactory system of insects. Orco as an obligatory subunit of ORs is highly conserved, providing an opportunity to systematically evaluate OR-dependent olfactory responses.

Results

Herein, we successfully established a homozygous mutant (Orco−/−) of Helicoverpa armigera, a notorious crop pest, using the CRISPR/Cas9 gene editing technique. We then compared the olfactory response characteristics of wild type (WT) and Orco−/− adults and larvae. Orco−/− males were infertile, while Orco−/− females were fertile. The lifespan of Orco−/− females was longer than that of WT females. The expressions of most Ors, Irs, and other olfaction-related genes in adult antennae of Orco−/− moths were not obviously affected, but some of them were up- or down-regulated. In addition, there was no change in the neuroanatomical phenotype of Orco−/− moths at the level of the antennal lobe (including the macroglomerular complex region of the male). Using EAG and SSR techniques, we discovered that electrophysiological responses of Orco−/− moths to sex pheromone components and many host plant odorants were absent. The upwind flight behaviors toward sex pheromones of Orco−/− males were severely reduced in a wind tunnel experiment. The oviposition selectivity of Orco−/− females to the host plant (green pepper) has completely disappeared, and the chemotaxis toward green pepper was also lost in Orco−/− larvae.

Conclusions

Our study indicates that OR-mediated olfaction is essential for pheromone communication, oviposition selection, and larval chemotaxis of H. armigera, suggesting a strategy in which mate searching and host-seeking behaviors of moth pests could be disrupted by inhibiting or silencing Orco expression.
Mucosal-associated invariant T cells predict increased acute graft-versus-host-disease incidence in patients receiving allogeneic hematopoietic stem cell transplantation
Authors: Wang Zhao , Zhang Sudong , Zhang Xiaoyu , Liu Li , Zhou Lukun , Shen Yuyan , Zhang Rongli , He Yi , Yang Donglin , Jiang Erlie , Feng Xiaoming , Zhou Jiaxi , Cheng Tao , Han Mingzhe , Feng Sizhou
Published: September 2022

Background

Mucosal-associated invariant T (MAIT) cells are innate-like T cells, some studies have reported that the number of circulating MAIT cells reduced in patients with acute graft-versus-host-disease (aGVHD) development. However, the role of donor MAIT cells on aGVHD development and subsequent functional change still remain unclear.

Methods

The study recruited 86 patients with hematological malignancies who underwent allogeneic hematopoietic cell transplantation (HCT) from May 1, 2018 to June 30, 2019. MAIT cells, their subset, and cytokine levels were measured by flow cytometry. Gray’s test was used to assess the impact of graft MAIT cell proportion and number on aGVHD incidence. The Cox proportional hazard model was used in the multivariate analysis. The comparison for continuous variables was assessed using Mann–Whitney analysis. RNA-sequencing was performed to investigate the possible molecular pathway changes.

Results

Our study showed that the proportion of MAIT cells in grafts was not different from normal controls, but the CD4/8 subsets were altered. Taking the median of the proportion and number of MAIT cells in the graft as the threshold, the results showed that the incidence of grade B-D aGVHD in patients with MAIT cell proportion ≥ 3.03% was significantly higher than that in patients with MAIT cell proportion < 3.03% (56.3%, 95% CI 37.1–71.2 versus 23.1%, 95% CI 13.8–46.2; P = 0.038).The number of MAIT cells in the graft was not associated with aGVHD development (P = 0.173), however, when the graft contained more CD4 positive, CD8 positive, and CD4/CD8 double-positive MAIT cells, the incidence of aGVHD was significantly increased (P = 0.019, P = 0.035 and P = 0.027, respectively). Besides, reduced frequencies and counts of circulating MAIT cells were observed in patients with aGVHD when compared to patients without aGVHD, accompanied by enhanced production of Tumor necrosis factor-α, Interferon-γ and upregulated programmed death-1, CXC Chemokine Receptor-6 (CXCR6) and CD38 expression. Gene set enrichment analysis of MAIT cell RNA-seq data showed interferon-α response pathway upregulated in aGVHD patients when compared with patients without aGVHD and healthy controls.

Conclusions

Our study shows that MAIT cells in grafts and peripheral blood are both closely related to the aGVHD development post allogeneic HCT. Interferon-α response pathway perhaps is a critical regulation mechanism for the MAIT cell involvement in aGVHD development.
The prognostic value of the previous nephrectomy in pretreated metastatic renal cell carcinoma receiving immunotherapy: a sub-analysis of the Meet-URO 15 study
Authors: Rebuzzi Sara Elena , Signori Alessio , Banna Giuseppe Luigi , Gandini Annalice , Fornarini Giuseppe , Damassi Alessandra , Maruzzo Marco , De Giorgi Ugo , Basso Umberto , Chiellino Silvia , Galli Luca , Zucali Paolo Andrea , Fantinel Emanuela , Naglieri Emanuele , Procopio Giuseppe , Milella Michele , Boccardo Francesco , Fratino Lucia , Pipitone Stefania , Ricotta Riccardo , Panni Stefano , Mollica Veronica , Sorarù Mariella , Santoni Matteo , Cortellini Alessio , Prati Veronica , Soto Parra Hector Josè , Santini Daniele , Atzori Francesco , Di Napoli Marilena , Caffo Orazio , Messina Marco , Morelli Franco , Prati Giuseppe , Nolè Franco , Vignani Francesca , Cavo Alessia , Roviello Giandomenico , Rescigno Pasquale , Buti Sebastiano
Published: September 2022

Background

Nephrectomy is considered the backbone of managing patients with localized and selected metastatic renal cell carcinoma (mRCC). The prognostic role of nephrectomy has been widely investigated with cytokines and targeted therapy, but it is still unclear in the immunotherapy era.

Methods

We investigated the Meet-URO-15 study dataset of 571 pretreated mRCC patients receiving nivolumab as second or further lines about the prognostic role of the previous nephrectomy (received in either the localized or metastatic setting) in the overall population and according to the Meet-URO score groups.

Results

Patients who underwent nephrectomy showed a significantly reduced risk of death (HR 0.44, 95% CI 0.32–0.60, p < 0.001) with a longer median overall survival (OS) (35.9 months vs 12.1 months), 1-year OS of 71.6% vs 50.5% and 2-years OS of 56.5% vs 22.0% compared to those who did not. No significant interaction between nephrectomy and the overall five Meet-URO score risk groups was observed (p = 0.17). It was statistically significant when merging group 1 with 2 and 3 and group 4 with 5 (p = 0.038) and associated with a longer OS for the first three prognostic groups (p < 0.001), but not for groups 4 and 5 (p = 0.54).

Conclusions

Our study suggests an overall positive impact of the previous nephrectomy on the outcome of pretreated mRCC patients receiving immunotherapy. The clinical relevance of cytoreductive nephrectomy, optimal timing and patient selection deserves further investigation, especially for patients with Meet-URO scores of 1 to 3, who are the once deriving benefit in our analyses. However, that benefit is not evident for IMDC poor-risk patients (including the Meet-URO score groups 4 and 5) and a subgroup of IMDC intermediate-risk patients defined as group 4 by the Meet-URO score.
Inhibition of XPO1 with KPT-330 induces autophagy-dependent apoptosis in gallbladder cancer by activating the p53/mTOR pathway
Authors: Zhao Cheng , Yang Zi-yi , Zhang Jian , Li Ou , Liu Shi-lei , Cai Chen , Shu Yi-jun , Pan Li-jia , Gong Wei , Dong Ping
Published: September 2022

Background

Gallbladder cancer (GBC) is a highly aggressive malignant cancer in the biliary system with poor prognosis. XPO1 (chromosome region maintenance 1 or CRM1) mediates the nuclear export of several proteins, mainly tumor suppressors. Thus, XPO1 functions as a pro-oncogenic factor. KPT-330 (Selinexor) is a United States Food and Drug Administration approved selective inhibitor of XPO1 that demonstrates good therapeutic effects in hematologic cancers. However, the function of XPO1 and the effect of KPT-330 have not been reported in GBC.

Methods

We analyzed the correlation between XPO1 expression levels by q-PCR and clinical features of GBC patients. Cell proliferation assays were used to analyze the in vitro antitumor effects of XPO1 inhibitor KPT-330. mRNA sequencing was used to explore the underlying mechanisms. Western blot was performed to explore the relationship between apoptosis and autophagy. The in vivo antitumor effect of KPT-330 was investigated in a nude mouse model of gallbladder cancer.

Results

We found that high expression of XPO1 was related to poor prognosis of GBC patients. We observed that XPO1 inhibitor KPT-330 inhibited the proliferation of GBC cells in vitro. Furthermore, XPO1 inhibitor KPT-330 induced apoptosis by reducing the mitochondrial membrane potential and triggering autophagy in NOZ and GBC-SD cells. Indeed, XPO1 inhibitor KPT-330 led to nuclear accumulation of p53 and activated the p53/mTOR pathway to regulate autophagy-dependent apoptosis. Importantly, KPT-330 suppressed tumor growth with no obvious toxic effects in vivo.

Conclusion

XPO1 may be a promising prognostic indicator for GBC, and KPT-330 appears to be a potential drug for treating GBC effectively and safely.
Concomitant medication of cetirizine in advanced melanoma could enhance anti-PD-1 efficacy by promoting M1 macrophages polarization
Authors: Mallardo Domenico , Simeone Ester , Vanella Vito , Vitale Maria Grazia , Palla Marco , Scarpato Luigi , Paone Miriam , De Cristofaro Teresa , Borzillo Valentina , Cortellini Alessio , Sparano Francesca , Pignata Sandro , Fiore Francesco , Caracò Corrado , Maiolino Piera , Petrillo Antonella , Cavalcanti Ernesta , Lastoria Secondo , Muto Paolo , Budillon Alfredo , Warren Sarah , Ascierto Paolo Antonio
Published: September 2022

Background

The clinical observation showed a potential additive effect of anti-PD-1 agents and cetirizine in patients with advanced melanoma.

Methods

Clinical outcomes of concomitant cetirizine/anti-PD-1 treatment of patients with stage IIIb–IV melanoma were retrospectively collected, and a transcriptomic analysis was performed on blood samples obtained at baseline and after 3 months of treatment.

Results

Patients treated with cetirizine concomitantly with an anti-PD-1 agent had significantly longer progression-free survival (PFS; mean PFS: 28 vs 15 months, HR 0.46, 95% CI: 0.28–0.76; p = 0.0023) and OS (mean OS was 36 vs 23 months, HR 0.48, 95% CI: 0.29–0.78; p = 0.0032) in comparison with those not receiving cetirizine. The concomitant treatment was significantly associated with ORR and DCR (p < 0.05). The expression of FCGR1A/CD64, a specific marker of macrophages, was increased after the treatment in comparison with baseline in blood samples from patients receiving cetirizine, but not in those receiving only the anti-PD1, and positively correlated with the expression of genes linked to the interferon pathway such as CCL8 (rho = 0.32; p = 0.0111), IFIT1 (rho = 0.29; p = 0.0229), IFIT3 (rho = 0.57; p < 0.0001), IFI27 (rho = 0.42; p = 0.008), MX1 (rho = 0.26; p = 0.0383) and RSAD2 (rho = 0.43; p = 0.0005).

Conclusions

This retrospective study suggests that M1 macrophage polarization may be induced by cetirizine through the interferon-gamma pathway. This effect may synergize with the immunotherapy of advanced melanoma with anti-PD-1 agents.
LAG3 blockade coordinates with microwave ablation to promote CD8+ T cell-mediated anti-tumor immunity
Authors: Shao Dong , Chen Yaping , Huang Hao , Liu Yingting , Chen Junjun , Zhu Dawei , Zheng Xiao , Chen Lujun , Jiang Jingting
Published: September 2022

Background

The immune checkpoint inhibitors (ICIs) combined with other therapeutic strategies have shown exciting results in various malignancies, and ICIs have now become the gold standard for current cancer treatment. In several preclinical and clinical investigations, ablation coupled with immunotherapy has proved to be quite effective. Our previous studies have shown that ablation coupled with ICI is a potential anti-cancer regimen for colorectal cancer liver metastases (CRLM). Furthermore, we have reported that following microwave ablation (MWA), the expression of LAG3 is up-regulated in tumor microenvironment (TME), indicating that LAG3 is implicated in the regulation of immunosuppressive immune response, and combination therapy of MWA and LAG3 blockade can serve as a promising therapeutic strategy against cancer.

Methods

The expression of LAG3 was investigated in this study utilizing a preclinical mouse model treated with MWA. Moreover, we monitored the tumor development and survival in mice to assess the anti-cancer effects of MWA alone or in combination with LAG3 blockade. Flow cytometry was also used to phenotype the tumor-infiltrating lymphocytes (TILs) and CD8+ T cell effector molecules. We finally analyzed the single-cell RNA sequencing (scRNA-seq) data of infiltrating CD45+ immune cells in the tumors from the MWA alone and MWA combined with LAG3 blockade groups.

Results

After MWA, the expression of LAG3 was up-regulated on sub-populations of TILs, and introducing LAG3 blockade to MWA postponed tumor development and extended survival in the MC38 tumor model. Flow cytometry and scRNA-seq revealed that LAG3 blockade in combination with MWA markedly boosted the proliferation and the function of CD8+ TILs, leading to altered myeloid cells in the TME.

Conclusion

Combination therapy of LAG3 blockade and MWA was a unique therapeutic regimen for some solid tumors, and such combination therapy might reprogram the TME to an anti-tumor manner.
Efficacy and safety of novel oral anticoagulants in patients with atrial nonvalvular atrial fibrillation and diabetes mellitus: a systematic review and meta-analysis
Authors: Jia Xuedong , Yin Zhao , Zhang Wan , Du Shuzhang , Kang Jian
Published: September 2022

Objective

This study incorporates the results of subgroup analyses of currently published randomized controlled trials (RCTs) and real-world cohort studies to compare the effectiveness and safety of new direct oral anticoagulants (NOACs) and warfarin among nonvalvular atrial fibrillation patients with diabetes.

Methods

The PubMed, Embase, Cochrane Library, Web of Science and ClinicalTrials.gov databases were searched. Five retrospective cohort studies and four subgroup analyses of RCTs were included in this meta-analysis.

Results

A meta-analysis of the data of 26,7272 patients showed that for patients with nonvalvular atrial fibrillation and diabetes, NOACs can significantly reduce the incidence of stroke/systemic embolism (SSE), ischaemic stroke, and haemorrhagic stroke compared with warfarin, with no significant difference in major bleeding and all-cause mortality. Additionally, NOACs were superior to warfarin in the incidence of intracranial bleeding, gastrointestinal bleeding, myocardial infarction, and vascular death.

Conclusions

Among nonvalvular atrial fibrillation patients with diabetes, NOACs were associated with a lower risk of SSE versus warfarin, with no significant difference in major bleeding. Therefore, NOACs may be a better clinical choice.
Immune-related 3-lncRNA signature with prognostic connotation in a multi-cancer setting
Authors: Sherif Shimaa , Mall Raghvendra , Almeer Hossam , Naik Adviti , Al Homaid Abdulaziz , Thomas Remy , Roelands Jessica , Narayanan Sathiya , Mohamed Mahmoud Gasim , Bedri Shahinaz , Al-Bader Salha Bujassoum , Junejo Kulsoom , Bedognetti Davide , Hendrickx Wouter , Decock Julie
Published: September 2022

Background

Advances in our understanding of the tumor microenvironment have radically changed the cancer field, highlighting the emerging need for biomarkers of an active, favorable tumor immune phenotype to aid treatment stratification and clinical prognostication. Numerous immune-related gene signatures have been defined; however, their prognostic value is often limited to one or few cancer types. Moreover, the area of non-coding RNA as biomarkers remains largely unexplored although their number and biological roles are rapidly expanding.

Methods

We developed a multi-step process to identify immune-related long non-coding RNA signatures with prognostic connotation in multiple TCGA solid cancer datasets.

Results

Using the breast cancer dataset as a discovery cohort we found 2988 differentially expressed lncRNAs between immune favorable and unfavorable tumors, as defined by the immunologic constant of rejection (ICR) gene signature. Mapping of the lncRNAs to a coding-non-coding network identified 127 proxy protein-coding genes that are enriched in immune-related diseases and functions. Next, we defined two distinct 20-lncRNA prognostic signatures that show a stronger effect on overall survival than the ICR signature in multiple solid cancers. Furthermore, we found a 3 lncRNA signature that demonstrated prognostic significance across 5 solid cancer types with a stronger association with clinical outcome than ICR. Moreover, this 3 lncRNA signature showed additional prognostic significance in uterine corpus endometrial carcinoma and cervical squamous cell carcinoma and endocervical adenocarcinoma as compared to ICR.

Conclusion

We identified an immune-related 3-lncRNA signature with prognostic connotation in multiple solid cancer types which performed equally well and in some cases better than the 20-gene ICR signature, indicating that it could be used as a minimal informative signature for clinical implementation.
Imaging markers of cerebral amyloid angiopathy and hypertensive arteriopathy differentiate Alzheimer disease subtypes synergistically
Authors: Chen Ting-Bin , Lee Wei-Ju , Chen Jun-Peng , Chang Shiang-Yu , Lin Chun-Fu , Chen Hung-Chieh
Published: September 2022

Background

Both cerebral amyloid angiopathy (CAA) and hypertensive arteriopathy (HA) are related to cognitive impairment and dementia. This study aimed to clarify CAA- and HA-related small vessel disease (SVD) imaging marker associations with cognitive dysfunction and Alzheimer disease (AD) subtypes.

Methods

A sample of 137 subjects with clinically diagnosed late-onset AD identified from the dementia registry of a single center from January 2017 to October 2021 were enrolled. Semi-quantitative imaging changes (visual rating scale grading) suggestive of SVD were analyzed singularly and compositely, and their correlations with cognitive domains and AD subtypes were examined.

Results

Patients with typical and limbic-predominant AD subtypes had worse cognitive performance and higher dementia severity than minimal-atrophy subtype patients. Deep white matter hyperintensity (WMH) presence correlated inversely with short-term memory (STM) performance. The three composite SVD scores correlated with different cognitive domains and had distinct associations with AD subtypes. After adjusting for relevant demographic factors, multivariate logistic regression (using minimal-atrophy subtype as the reference condition) revealed the following: associations of the typical subtype with periventricular WMH [odds ratio (OR) 2.62; 95% confidence interval (CI), 1.23–5.57, p = 0.012], global SVD score (OR 1.67; 95%CI, 1.11–2.52, p = 0.009), and HA-SVD score (OR 1.93; 95%CI, 1.10–3.52, p = 0.034); associations of limbic-predominant subtype with HA-SVD score (OR 2.57; 95%CI, 1.23–5.37, p = 0.012) and most global and domain-specific cognitive scores; and an association of hippocampal-sparing subtype with HA-SVD score (OR 3.30; 95%CI, 1.58–6.85, p = 0.001).

Conclusion

Composite SVD imaging markers reflect overall CAA and/or HA severity and may have differential associations with cognitive domains and AD subtypes. Our finding supports the possibility that the clinical AD subtypes may reflect differing burdens of underlying CAA and HA microangiopathologies.
Final-note expectancy and humor: an empirical investigation
Authors: Nagy Sándor Imre , Révész György , Séra László , Bandi Szabolcs Ajtony , Stachó László
Published: September 2022

Background

Melodic expectations were manipulated to investigate the nature of tonally incongruent melodic final notes that may elicit humor in listeners. To our knowledge, this is the first experiment aiming at studying humor elicitation in music with the use of empirical, quantitative methods. To this aim, we have based the experiment on the incongruency/resolution theory of humor and the violations of expectations in music. Our goal was to determine the amount of change, that is, the degree of incongruency required to elicit humor.

Methods

We composed two simple, 8-bar long melodies, and changed their final notes so that they could randomly finish on any semitone between an octave upwards and downwards with respect to the original, tonic final note. This resulted in 25 versions for both melodies, including the original final notes, for each semitone. Musician and non-musician participants rated each version of each melody on five 7-point bipolar scales according to goodness of fit, humor, beauty, playfulness, and pleasantness.

Results and conclusions

Our results showed that even a single change of the final note can elicit humor. No strong connection was found between humor elicitation and the level of incongruency (i.e., the amount of violation of expectation). Instead, changes to the major-mode melody were more likely to be found humorous than those to the minor-mode melody, implying that a so-called playful context is necessary for humor elicitation as the major melody was labelled playful by the listeners. Furthermore, final notes below the original tonic end note were also found to be less humorous and less fitting to the melodic context than those above it.
The implementation of an online mindfulness-based program for pediatric patients at a tertiary hospital in South America: a feasibility study protocol
Authors: Pasqualucci Paula , Seifert Georg , Filho Vicente Odone , dos Santos Angelica Carreira
Published: September 2022

Background

The prevalence of chronic and complex pediatric health conditions has quickly risen over the last decades. Chronic and complex health conditions make pediatric patients and their families more susceptible to many distressing events during their lifespan. Mindfulness-based interventions have become a popular intervention for individuals living with chronic illnesses and have been adapted for pediatric populations with good results, including online versions. This study intends to report an implementation protocol of an online mindfulness-based program for adolescents to address an important gap in stress relief and health promotion for pediatric patients.

Methods

In this article, we describe the rationale and design of an implementation study of an online mindfulness-based program for pediatric patients at a tertiary pediatric hospital in South America. Participants will be recruited during one year to participate in an eight-session online mindfulness-based program. To assess our primary aim of feasibility, we will exam recruitment, retention and participation rates. Participants will also complete a symptomatology evaluation (i.e., depression, anxiety, and stress symptoms) at baseline and immediately at post-treatment and fidelity will be evaluated by a structured questionnaire.

Discussion

This study will be the first known to assess the implementation of an online mindfulness-based program for a pediatric population at a tertiary pediatric center in South America under real-life conditions. This study will establish the feasibility of a novel intervention aimed at promoting mental health and positive coping strategies among pediatric patients with chronic and complex health conditions. Evidence from this study would be useful to patients, families, clinicians, and policymakers and will help to devise strategies of health promotion for the pediatric population, as well as serve as a model for a future trial to examine efficacy of the proposed intervention.

Trial registration

This research has been registered at Ensaiosclinicos.gov.br, identifier RBR-23trp87. Registered 25 February 2022—retrospectively registered.
Scanning laser ophthalmoscopy retroillumination: applications and illusions
Authors: Mainster Martin A. , Desmettre Thomas , Querques Giuseppe , Turner Patricia L. , Ledesma-Gil Gerardo
Published: September 2022

Scanning laser ophthalmoscopes (SLOs) are used widely for reflectance, fluorescence or autofluorescence photography and less commonly for retroillumination imaging. SLOs scan a visible light or near-infrared radiation laser beam across the retina, collecting light from each retinal spot as it’s illuminated. An SLO’s clinical applications, image contrast and axial resolution are largely determined by an aperture overlying its photodetector. High contrast, reflectance images are produced using small diameter, centered apertures (confocal apertures) that collect retroreflections and reject side-scattered veiling light returned from the fundus. Retroillumination images are acquired with annular on-axis or laterally-displaced off-axis apertures that capture scattered light and reject the retroreflected light used for reflectance imaging. SLO axial resolution is roughly 300 μm, comparable to macular thickness, so SLOs cannot provide the depth-resolved chorioretinal information obtainable with optical coherence tomography’s (OCT’s) 3 μm axial resolution. Retroillumination highlights and shades the boundaries of chorioretinal tissues and abnormalities, facilitating detection of small drusen, subretinal drusenoid deposits and subthreshold laser lesions. It also facilitates screening for large-area chorioretinal irregularities not readily identified with other en face retinal imaging modalities. Shaded boundaries create the perception of lesion elevation or depression, a characteristic of retroillumination but not reflectance SLO images. These illusions are not reliable representations of three-dimensional chorioretinal anatomy and they differ from objective OCT en face topography. SLO retroillumination has been a useful but not indispensable retinal imaging modality for over 30 years. Continuing investigation is needed to determine its most appropriate clinical roles in multimodal retinal imaging.
Intersectionality and the invisibility of transgender health in the Philippines
Authors: Abesamis Luis Emmanuel A.
Published: September 2022

Transgender (trans) Filipinos are disproportionately vulnerable to health problems because of the inaccessibility of essential healthcare services resulting from the invisibility and exclusion of trans health in Philippine health and related social institutions. Because of the institutional prejudice and discrimination against trans Filipinos in Philippine society, an intersectional approach presents an opportunity to analyze the invisibility and potentially elucidate the unique health needs of trans Filipinos. This article elucidates how the invisibility of trans Filipinos in health is a product of co-existing and interacting prejudiced and discriminatory institutions, such as the law, education, and medicine, where the historical experiences of colonization, the hegemony of cisgenderism, and the impact of capitalism remain salient. By elucidating these co-existing and interacting structures and forces, this article highlights the gaps in the Philippine healthcare system, such as the lack of affirming and protective policies for trans health and the limited cultural competence of healthcare providers. In light of these, future research and policy work must work towards integrating gender-specific and gender-inclusive approaches, centering the voices of trans Filipinos in health discourses, and decolonizing and expanding the local understanding of trans health among Filipinos.
Guillain–Barré syndrome variants: a grave complication of bariatric surgery
Authors: Aljthalin Raseel A. , Al-Attas Alawi A.
Published: September 2022

Background

Guillain–Barré syndrome is an acquired inflammatory disease of the peripheral nervous system. It is the most frequent cause of acute flaccid symmetrical weakness of the limbs and areflexia usually reaching its peak within a month.

Case presentation

Herein we report two post-bariatric surgery cases that presented with clinical pictures of Guillain–Barré syndrome based on their clinical and electrophysiological findings. Both patients were treated with intravenous immunoglobulin for 5 days. Both patients showed significant improvement and full recovery.

Conclusion

Guillain–Barré syndrome is a possible grave complication of bariatric surgery which needs prompt recognition and intervention.
Frequency-swept feedback interferometry for noncooperative-target ranging with a stand-off distance of several hundred meters
Authors: Wang Yifan , Xu Xin , Dai Zongren , Hua Ziyu , Lin Chenxiao , Hou Yubin , Zhang Qian , Wang Pu , Tan Yidong
Published: September 2022

Frequency-swept interferometry (FSI) is a powerful ranging method with high precision and immunity to ambient light. However, the stand-off distance of the current FSI-based ranging system for noncooperative targets is relatively short because the weak echo power cannot provide the needed signal-to-noise ratio (SNR). Here, we report a ranging method that combines FSI and the laser feedback technique. Compared with conventional FSI, the interference between the weak echo signal and the local oscillator occurs in the laser cavity, which enhances the signal spontaneously and then provides an improved SNR. In the experiments, the detection limit of the echo power is less than 0.1 fW, with a 1 mW probe beam. Based on the enhancement from the laser feedback technique, the system can detect a noncooperative target that is up to hundreds of meters away in space without extra optical amplifiers. On the other hand, a large stand-off distance makes the system sensitive to environmental disturbance, which degrades the ranging precision. To address this issue, an interferometry-based compensation device, which is also sensitive to weak echoes from noncooperative targets, is proposed to monitor the optical-path-length drifts and ensure accurate beat frequency recognition. Moreover, the device can record distance changes during the integration time of ranging and track a moving target precisely with improved temporal resolution. Owing to the high sensitivity and the validity of the compensation approach, the standard deviation in 10 measurements is better than 0.07 mm when targeting an aluminum sheet at approximately 152 m. Generally, with a large range, high relative precision, and low photon consumption, the novel technical scheme for laser ranging demonstrates new capabilities that promise to enable a wide range of applications, such as large equipment assembly and noncooperative-target tracking.
Flexure behavior of hollow steel beams strengthening with ferrocement
Authors: Elkassas Ehab , Morsy Alaa M. , Marzouck Mohamed
Published: September 2022

Experimental and numerical studies are carried out to investigate the flexural behavior of precast lightweight composite beams composed of a hollow steel beam strengthened with a ferrocement layer. This composite beam comprises of a slender cold-formed hollow section of dimension (140 × 180 mm) of different thicknesses surrounded by a ferrocement layer. This composite beam is named a precast ferrocement cold-formed hollow section (FCH). Nine beams with a span of 1500 mm were tested under a four-point bending system to evaluate their flexural strength. Four different parameters have been examined, which are the spacing of shear connectors, ferrocement thickness, hollow steel section thickness, and the effect of surface friction. The test results showed that the presence of 30 mm ferrocement layer increased the capacity by 18% compared with the control specimen. The presence of shear connectors increases the capacity by 30%. Increasing the steel cross-section thicknesses increase section capacity by 16–33% and finally, increasing the surface friction has a very small effect on the section capacity, which can be neglected. The finite element models were developed and validated by the test results; results show a close agreement between the experimental and finite element results. Extensive parameters were investigated, which were mortar compressive strength (f'c) and the position of the shear connectors. The results indicated that increasing mortar strength increases section capacity ranging between 11% and 18%. The presence of a shear connector in the web and the lower flange of the hollow section have an insignificant effect.
Predictors of compliance with payer-led oncology clinical pathways.
Authors: Mullangi Samyukta , Chen Xiaoxue , Pham Timothy , Liu Ying , Gordon Aliza , Debono David Joseph , Fisch Michael Jordan , Gonen Mithat , Hershman Dawn L.
Published: September 2022

7

Background: Rising healthcare costs have garnered interest from payers in shifting oncology care towards a value-based practice model. Pathways are a subset of evidence-based guidelines designed to standardize cancer drug prescribing by clarifying decisions along three priorities: efficacy, safety, and cost. However, the major predictors of compliance with clinical pathway recommendations are unknown. Methods: We conducted a retrospective cohort study using administrative claims linked with prior authorization data of Anthem commercial and Medicare Advantage members. We identified members aged 18 or older with a diagnosis of breast, lung, colorectal, bladder, kidney, uterine, pancreatic cancer or melanoma being treated with a first-line treatment regimen in the metastatic setting between July 2018 and October 2021. The primary outcome was pathway compliance (PC), defined as whether a patient’s anti-cancer drug regimen is also an Anthem pathway-endorsed regimen. We built a logistic regression model with stepwise backward selection to identify patient, physician, practice, geographic, and temporal factors that were associated with PC. Results: The cohort comprised 17,584 patients in total. The treatment period yielded 11,277 (64%) observations of patients with PC (48.1% male, mean [SD] age 60.7 years [11]) and 6,307 (36%) without PC (45.1% male, mean [SD] age 60.4 years [11.6]). In adjusted analyses, we find that the odds of PC decrease over time and with variation by malignancy. Any inpatient (OR = 1.32, 95% CI 1.22 – 1.43) or emergency room utilization (OR = 1.21, 95% CI 1.12 – 1.31) in the baseline 6-month period was associated with a higher odds of PC. Conversely, doubling total medical costs in the preceding 6 months was associated with lower odds of PC (OR 0.86, 95% CI 0.83 – 0.88). The odds of PC increased with a higher share (median or above vs below median) of Anthem patients per physician (OR 1.12, 95% CI 1.04 – 1.20). Finally, Oncology Care Model participation was associated with higher odds of PC (OR = 1.13 95% CI 1.04 – 1.23). Conclusions: Among patients treated in the first-line setting for metastatic disease, PC was observed in slightly under two-thirds of cases and was associated with the penetration of Anthem patients in the practice. Participation in OCM was also associated with increased PC. These findings would be of interest to policymakers focused on value-based cancer care.
The financial impact of reducing drug waste with biosimilar transition of trastuzumab in the Oncology Care Model for the U.S. Oncology Network.
Authors: Fernandez Jennifer , Indurlal Puneeth , Garey Jody S. , Dave Neal , Cleveland Richard , Agena Jody , Malhotra Rajat , Wilfong Lalan S.
Published: September 2022

11

Background: The Oncology Care Model (OCM), a 6-year long Medicare value-based care program, rewards practices for decreasing total cost of care (TCOC) compared to a benchmark price, while maintaining high quality cancer care. Care services for enrolled patients are divided into 6-month episodes within 1-year time intervals called Performance Periods (PP). One approach to reducing TCOC is reducing the expenditure for drug waste. In mid-2017, trastuzumab (HER2-targeted monoclonal antibody) 420 mg multi-dose vial (MDV) was discontinued and replaced with a 150 mg single-dose vial (SDV), leading to wastage of the remaining partial quantities of the SDV after preparation of a patient-defined dose. The increased drug waste led to an increase in the total drug cost of trastuzumab and TCOC. Late 2019, MDV and SDV biosimilar trastuzumab products were introduced, and The US Oncology Network (The Network) practices adopted the MDV biosimilar as a strategy to reduce drug waste and TCOC. This study highlights the impact of trastuzumab drug waste on TCOC. Methods: Claims data for 14 Network practices, participating in OCM, were assessed. The financial impact of drug waste and TCOC for The Network’s transition from MDV trastuzumab to SDV trastuzumab in 2017, and from SDV trastuzumab to the MDV biosimilar trastuzumab in 2020 was evaluated. Results: With the use of MDV trastuzumab during OCM PP1, drug waste accounted for 0.05% of the total dose of trastuzumab. After having to shift from MDV to SDV during PP2, as a result of the packaging change, trastuzumab drug waste increased to 10.25% of the total dose, with an increase in TCOC by 0.25% ($2M) per PP during PPs 3-7. As The Network practices adopted the use of MDV biosimilar trastuzumab starting in PP8, drug waste declined 57% to 4.4% of the total dose in PP9, reducing the drug waste component of TCOC by $1.4M (0.16%). Had all SDV trastuzumab doses been transitioned to the MDV biosimilar, an additional $600K (0.09%) in TCOC could have been reduced in PP9. Conclusions: TCOC fluctuations can be driven by not just increasing costs or increased utilization, but also by drug packaging and increasing drug waste. The discontinuation of MDV trastuzumab resulted in a substantial financial impact on drug waste, TCOC, and cost for patients. Swift transition to biosimilar MDV trastuzumab within The Network helped to significantly reduce drug waste and its impact on TCOC in the OCM. Trastuzumab biosimilars, in addition to being cost-effective alternatives to biological therapeutics, offer significant cost savings via drug waste reduction.
Real-world cost effectiveness of first-line pembrolizumab for advanced melanoma: A population-based study by the Canadian Real-world Evidence Value for Cancer Drugs (CanREValue) Collaboration.
Authors: Hanna Timothy , Aktar Suriya , Arciero Vanessa , Liu Ning , Chan Kelvin K.
Published: September 2022

17

Background: Randomized controlled trials (RCTs) demonstrate large survival benefits with anti-PD-1 checkpoint inhibitors compared to anti-CTLA4 therapy for advanced melanoma. However, it remains unclear if patients in routine practice derive a similar survival benefit or if real-world health utilization differs from trials. Outcomes are needed to inform life-cycle health technology reassessment (HTA) with real-world cost-effectiveness analysis. Methods: This study compared patients with advanced melanoma treated with publicly funded first-line ipilimumab (September 2012 - December 2014) or pembrolizumab (June 2016 - March 2018) in Ontario, Canada. These periods were chosen to reflect distinct eras of access to treatment. Linked administrative databases were used to identify cases, covariates, health-utilization and all-cause death. Inverse probability of treatment weighting (IPTW) with stabilizing weights was used to adjust for covariates (including: age, sex, melanoma site, rurality, income, comorbidity, stage at diagnosis, cancer history, prior brain metastasis treatment). Using a three-year time horizon, individual patient-level censoring-adjusted costs in 2019 Canadian dollars with a 1.5% annual discount rate were determined from the public payer’s perspective. The outcome was quality-adjusted life-years (QALY) measured at the individual patient level. Health utilities were based on accepted Canadian values from the initial HTA. The incremental cost-effectiveness ratio (ICER) was determined with bootstrap confidence intervals (CI). Results: Ninety patients treated with first-line ipilimumab, and 300 with pembrolizumab were identified. Those receiving pembrolizumab were older (median 70 vs.63 years), more likely to have multiple comorbidities (12% vs. 8%), and no prior brain radiation (83% vs. 74%). Covariates were balanced after weighting. Pembrolizumab was associated with improved OS (43.1% vs. 22.1% with ipilimumab at 3 years, IPTW adjusted hazard ratio: 0.52, 95% CI: 0.39-0.70; p < 0.001). Mean costs for pembrolizumab and ipilimumab were $212,706 (95% CI 196,122 - 229,290) and $158,352 ($143,218 - 173,484), and mean survival 1.20 QALY (95%CI 1.11 – 1.29) and 0.66 QALY (0.52 – 0.80) respectively. The ICER was $101,183/QALY (65,375 – 139,298). The probability of cost-effectiveness was 0%, 48% and 99% at willingness-to-pay thresholds of $50k, $100k and $150k respectively. Conclusions: In real-world patients, first-line pembrolizumab for advanced melanoma was associated with improved OS compared to ipilimumab. The real-world cost-effectiveness estimate of $101,183/QALY is similar to the model-based cost-effectiveness estimates ($114,389/QALY to $151,369/QALY) used in the initial health technology assessment recommendation prior to reimbursement.