bluuebunny/crossref_metadata_2025_split huggingface dataset:
How is pain associated with pelvic mesh implants measured? Refinement of the construct and a scoping review of current assessment tools
Authors: Todd Jennifer , Aspell Jane E. , Lee Michael C. , Thiruchelvam Nikesh 
Published: September 2022

Abstract
Background
Recommendations for the management of pain related to pelvic mesh implants are still under development. One limitation that has impeded progress in this area is that mesh-related pain has not been consistently defined or measured. Here, we reviewed the ways in which pain associated with pelvic mesh implants has been measured, and mapped the ways in which these existing measures capture the construct.

Methods
First, we reviewed existing accounts of the pain associated with pelvic mesh implants to develop a multifaceted construct definition, which includes aspects related to pain intensity, timing, body location, phenomenological qualities, impact/interference with daily living, and patient expectations and beliefs. Next, we reviewed the ways that the construct has been measured in the extant literature.

Results
Within 333 eligible studies, 28 different assessments of pain associated with pelvic mesh were identified, and 61% of studies reported using more than one measurement tool. Questionnaire measures included measures designed to assess urological and/or pelvic symptoms, generic measures and unvalidated measures. We did not identify any validated questionnaire measures designed to assess pain associated with pelvic mesh implants. The phenomenological, location, and expectation/belief components of the construct were not captured well by the identified questionnaire measures, and there is no evidence that any of the identified measures have appropriate psychometric properties for the assessment of pain related to pelvic mesh implants.

Conclusions
We recommend further qualitative research regarding women’s experiences of pelvic mesh-related pain assessment, and the development of a condition-specific patient reported outcome measure.
Novel mechanism of napabucasin, a naturally derived furanonaphthoquinone: apoptosis and autophagy induction in lung cancer cells through direct targeting on Akt/mTOR proteins
Authors: Petsri Korrakod , Thongsom Sunisa , Racha Satapat , Chamni Supakarn , Jindapol Saresa , Kaekratoke Nantawat , Zou Hongbin , Chanvorachote Pithi 
Published: September 2022

AbstractBackgroundAkt and mTOR are aberrantly activated in cancers and targeting these proteins are interesting for cancer drug discovery. Napabucasin (NB), a phytochemical compound, has been reported as potential anti-cancer agent, however, Akt and mTOR targeting mechanisms remain unclear. MethodApoptosis induction was investigated by Hoechst 33342/PI double staining and annexin V/PI staining with flowcytometry. Autophagy was evaluated by monodansylcadaverine staining and Western blot analysis. Binding affinity of NB and essential signaling proteins (PI3K, Akt, and mTOR) was investigated using molecular docking and confirmed by Western blot analysis.ResultA structure modification from changing methyl moiety of acetyl group of NB to hydroxyl moiety of carboxyl group of NB derivative (napabucasin-acid or NB-acid) greatly affected the compound activities. NB showed more potent anti-cancer activity. NB reduced cell viability with an approximately 20 times lower IC50and inhibited the colony formation capacity much more than NB-acid treated cells. NB induced cell apoptosis, which was accompanied by decrease Bcl‑2 and Mcl-1 and clevage of PARP, while NB-acid show lesser effect on Mcl-1. NB was found to strongly induce autophagy indicated by acidic vesicle staining and the LC3B conversion. Interestingly, computational molecular docking analysis further demonstrated that NB directly bound to Akt and mTOR (complex 1 and 2) proteins at their critical sites indicating that NB targets the upstream regulators of apoptosis and autophagy. The docking results were confirmed by decrease of p-Akt/Akt, p-mTOR/mTOR, and c-Myc a downstream target of Akt protein levels.ConclusionResults show for the first time that NB exerts an anti-cancer activity through the direct interaction to Akt and mTOR proteins. The methyl moiety of acetyl group of NB is required for its potent anti-cancer activities. These data encourage further development of NB compounds for Akt and mTOR driven cancers.
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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.