bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition effect of choline and parecoxib sodium on chronic constriction nerve injury-induced neuropathic pain in rats
Authors: Zhang Na , Li Yang , Feng Zeguo 
Published: January 2023

Abstract
Purpose
The simultaneous use of drugs with different mechanisms of analgesic action is a strategy for achieving effective pain control while minimizing dose-related side effects. Choline was described to potentiate the analgesic action of parecoxib sodium at small doses in several inflammatory pain models. However, these findings are still very limited, and more associated data are required to confirm the effectiveness of the combined choline and parecoxib sodium therapy against inflammatory pain.

Methods
Adult rats were randomly divided into 9 groups (N = 6/group). The sham surgery group received an intraperitoneal (i.p.) injection of saline. Rats with chronic constriction injury (CCI) of the sciatic nerve received saline, choline (cho, 6, 12 and 24 mg/kg), parecoxib sodium (pare, 3, 6, and 12 mg/kg), or a combination of choline 6 mg/kg and parecoxib sodium 3 mg/kg. Mechanical and heat pain thresholds were measured at 30 min after drug treatment at Days 3, 5, 7, 10, and 14 after CCI. Another 30 rats were divided into 5 groups (N = 6/group): the sham, CCI + saline, CCI + cho-6 mg/kg, CCI + pare-3 mg/kg, and CCI + cho-6 mg/kg + pare-3 mg/kg groups. After repeated drug treatment for 7 days, five rats were randomly selected from each group, and the lumbar dorsal root ganglia (DRGs) (L4–6) were harvested for western blot analysis.

Results
Choline significantly attenuated mechanical and heat hypersensitivity in CCI rats at 12 and 24 mg/kg doses (P < 0.05) but was not effective at the 6 mg/kg dose. Parecoxib sodium exerted significant pain inhibitory effects at the 6 and 12 mg/kg doses (P < 0.05) but not at the 3 mg/kg dose. Combining a low dose of choline (6 mg/kg) and parecoxib sodium (3 mg/kg) produced significant pain inhibition in CCI rats and reduced the expression of high mobility group protein 1 (HMGB1) and nuclear factor-kappa Bp65 (NF-κBp65) in L4–6 DRGs.

Conclusion
1. In a rat model of chronic neuropathic pain (CCI), at a certain dose, choline or parecoxib sodium can alleviate mechanical pain and thermal hyperalgesia caused by CCI. 2. The combination of choline and parecoxib sodium in nonanalgesic doses can effectively relieve neuropathic pain, and its mechanism may be related to the inhibition of the high mobility group protein 1 (HMGB1)/Toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) pathway.
Overexpression of TPM4 is associated with worse prognosis and immune infiltration in patients with glioma
Authors: Li Yao , Zhang Yanan , Wu Zeyu , Sun Peng 
Published: January 2023

Abstract

Background
Tropomyosin 4 (TPM4), a member of the tropomyosin family, is aberrantly expressed and plays an important role in a variety of cancers. However, studies on TPM4 in glioma patients are currently lacking.

Objective
Our study aimed to evaluate the diagnostic and prognostic characteristics of TPM4 in glioma and its correlation with immune infiltration.

Methods
Bioinformatic analysis was performed to determine whether TPM4 has diagnostic and prognostic value for glioma. The following databases and analytical tools were used to explore the clinical significance of TPM4 in glioma: TCGA, GTEx, GEO, STRING, and TISIDB.

Results
Our study showed that the mRNA and protein expression levels of TPM4 were significantly higher in glioma than in healthy brain tissue. Kaplan–Meier analysis indicated that high expression of TPM4 in glioma correlated with poor prognosis. Univariate Cox analysis indicated that the high expression level of TPM4 in glioma was an independent prognostic characteristic for low overall survival (OS). The areas under the 1-year survival ROC, 2-year survival ROC, and 3-year survival ROC were all greater than 0.8. GO and KEGG enrichment analysis and GSEA showed that humoral immune response and cytokine receptor interaction were significantly enriched in the TPM4 high expression group, where M phase of the cell cycle, neutrophil degranulation, signaling by interleukins, and signaling by rho GTPases were significantly enriched. Furthermore, according to the analysis of immune cell infiltration, TPM4 was associated with tumor infiltration of a variety of immune cells.

Conclusions
In conclusion, our study suggests that TPM4 may be an effective prognostic biomarker for glioma patients, providing new ideas and research directions for glioma research.
Umbrella review of basket trials testing a drug in tumors with actionable genetic biomarkers
Authors: Haslam Alyson , Olivier Timothée , Tuia Jordan , Prasad Vinay 
Published: January 2023

Abstract
Background
The utilization of basket trials in oncology has gained popularity because of the drive for precision medicine and the increasing ease of genetically profiling tumors. However, it is unknown if this has translated into patient benefit, either through higher response rates because of precision treatment or because of increasing options for less-common tumor types that are less represented in oncology drug trials. We sought to characterize basket studies for oncology drugs targeting a genetic biomarker, determine the responses for various tumor types and genetic biomarkers, and test for correlation between the number of participants in each tumor basket and the incidence of the respective tumor.

Methods
We conducted a retrospective cross-sectional review of oncology basket trials on Embase or clinicaltrials.gov with published data. We included studies that reported on oncology drugs that target a genetic biomarker. We examined the response for basket trial participants, stratified by tumor type and genetic biomarker and the correlation between the number of participants in each tumor basket and the incidence of the respective tumor.

Results
The overall response rate for all 25 included trials was 23%. The response for each genetic biomarker ranged from 0 to 69%, and for half of the genetic biomarkers, the response rate ranged from 0 to 100%, depending on tumor type. There is low correlation between the number of participants in each tumor basket and the incidence of the respective tumor (66.41 + -0.20x, R2 = 0.003, p = 0.75).

Conclusion
While there has been an increase in the number of published basket trials and individuals included in these trials, the response rate is low, but varies widely, depending on tumor type and genetic biomarker.
Evolution of treatment patterns and survival outcomes in patients with advanced non-small cell lung cancer treated at Frankfurt University Hospital in 2012–2018
Authors: Wolf Andrea , Stratmann Jan A. , Shaid Shabnam , Niklas Nicolas , Calleja Alan , Ubhi Harveen , Munro Robin , Waldenberger Daniela , Carroll Robert , Daumont Melinda J. , Penrod John R. , Lacoin Laure , Rohde Gernot 
Published: January 2023

Abstract
Background
Immune checkpoint inhibitors (ICIs) have improved outcomes for patients with advanced non-small cell lung cancer (NSCLC) versus chemotherapy in clinical trials. In Germany, ICIs have been used clinically since 2015 for patients with advanced/metastatic NSCLC without epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK) aberrations. As part of I-O Optimise, a multinational research program utilizing real-world data on thoracic malignancies, we describe real-world treatment patterns and survival following reimbursement of ICIs for advanced NSCLC in Germany.

Methods
This retrospective cohort study included patients with locally advanced/metastatic NSCLC without known EGFR/ALK aberrations who received a first line of therapy at Frankfurt University Hospital between January 2012 and December 2018, with follow-up to December 2019 or death, whichever occurred first. Using electronic medical records, treatment patterns and survival outcomes were described by histology (squamous cell [SQ]; non-squamous cell [NSQ]/other) and time period (pre- and post-ICI approval).

Results
Among eligible patients who started first-line treatment, 136 (pre-ICI) and 126 (post-ICI) had NSQ/other histology, and 32 (pre-ICI) and 38 (post-ICI) had SQ histology. Use of an ICI in the NSQ/other cohort increased from 5.9% (all second- or third-line) in the pre-ICI period to 57.1% (22.2% in first-line, including 13.5% as monotherapy and 8.7% combined with chemotherapy) in the post-ICI period. This was paralleled by a significant (P < 0.0001) prolongation of median (95% CI) OS from 9.4 (7.1–11.1) to 14.8 (12.7–20.5) months between the pre-ICI and post-ICI periods. A similar increase in the uptake of ICI was observed for the SQ cohort (from 3.1% pre-ICI [fourth-line] to 52.6% post-ICI [28.9% as first-line, including 15.8% as monotherapy and 13.2% combined with chemotherapy]); however, analysis of survival outcomes was limited by small group sizes.

Conclusion
These real-world data complement clinical trial evidence on the effectiveness of ICIs in patients with advanced NSCLC and NSQ/other histology in Germany.
Face-to-face and online teaching experience on experimental animals and alternative methods with nursing students: a research study
Authors: Garcia Sierra Juan F. , Fernandez Martinez M. Nélida , Lopez Cadenas Cristina , Diez Laiz Raquel , Rodriguez Lago José M. , Sahagun Prieto Ana M. 
Published: January 2023

Abstract
Background
Animal models are increasingly used in Nursing science to study care approaches. Despite the scientific relevance and the ethical debate surrounding the use of experimental animals, there is a scarcity of scholarly literature exploring this topic in Nursing Schools.

Aim
To evaluate perceptions and attitudes of nursing students enrolled in a Pharmacology course on the use of experimental animals and implementation of alternative methods, by comparing the experience for two academic years. An interdisciplinary collaboration has also been developed.

Methods
A descriptive cross-sectional, quantitative study was developed. Undergraduate nursing students were enrolled in the Pharmacology subject at the University of Leon (Spain). The study was carried out in the Pharmacology facilities. Students followed a two-session practical class regarding experimental animals and alternative methods in the Pharmacology course (Degree in Nursing) in two different academic years (2019–20/2020–21). At the end of the activity, they answered a questionnaire to assess their opinions on the use of experimental animals and alternative methods in Pharmacology and the 3Rs principle.

Results
A comparison of the students’ perception with and without direct participation in the evaluation of promazine effects in mice was made. A total of 190 students participated in the teaching experience, providing high scores in all items (4–5 out of 5 points) regarding the teaching experience. Students became also aware of the advantages and disadvantages on the use of experimental animals, as well as the ethical considerations to bear in mind for their use and the need for alternative methods.

Conclusions
In the students’ opinion, the total replacement of animals by alternative techniques was very difficult, and they preferred to do the practice face-to-face. The alternative method designed was useful for the students to accept the employment of experimental animals in biomedical research and education, and know the legislation applied in the protection of animals.
Inhibition of histone deacetylase 6 destabilizes ERK phosphorylation and suppresses cancer proliferation via modulation of the tubulin acetylation-GRP78 interaction
Authors: Wattanathamsan Onsurang , Chantaravisoot Naphat , Wongkongkathep Piriya , Kungsukool Sakkarin , Chetprayoon Paninee , Chanvorachote Pithi , Vinayanuwattikun Chanida , Pongrakhananon Varisa 
Published: January 2023

AbstractBackgroundThe leading cause of cancer-related mortality worldwide is lung cancer, and its clinical outcome and prognosis are still unsatisfactory. The understanding of potential molecular targets is necessary for clinical implications in precision diagnostic and/or therapeutic purposes. Histone deacetylase 6 (HDAC6), a major deacetylase enzyme, is a promising target for cancer therapy; however, the molecular mechanism regulating cancer pathogenesis is largely unknown.MethodsThe clinical relevance of HDAC6 expression levels and their correlation with the overall survival rate were analyzed based on the TCGA and GEO databases. HDAC6 expression in clinical samples obtained from lung cancer tissues and patient-derived primary lung cancer cells was evaluated using qRT–PCR and Western blot analysis. The potential regulatory mechanism of HDAC6 was identified by proteomic analysis and validated by immunoblotting, immunofluorescence, microtubule sedimentation, and immunoprecipitation-mass spectrometry (IP-MS) assays using a specific inhibitor of HDAC6, trichostatin A (TSA) and RNA interference to HDAC6 (siHDAC6). Lung cancer cell growth was assessed by an in vitro 2-dimensional (2D) cell proliferation assay and 3D tumor spheroid formation using patient-derived lung cancer cells.ResultsHDAC6 was upregulated in lung cancer specimens and significantly correlated with poor prognosis. Inhibition of HDAC6 by TSA and siHDAC6 caused downregulation of phosphorylated extracellular signal-regulated kinase (p-ERK), which was dependent on the tubulin acetylation status. Tubulin acetylation induced by TSA and siHDAC6 mediated the dissociation of p-ERK on microtubules, causing p-ERK destabilization. The proteomic analysis demonstrated that the molecular chaperone glucose-regulated protein 78 (GRP78) was an important scaffolder required for p-ERK localization on microtubules, and this phenomenon was significantly inhibited by either TSA, siHDAC6, or siGRP78. In addition, suppression of HDAC6 strongly attenuated an in vitro 2D lung cancer cell growth and an in vitro 3D patient derived-lung cancer spheroid growth.ConclusionsHDAC6 inhibition led to upregulate tubulin acetylation, causing GRP78-p-ERK dissociation from microtubules. As a result, p-ERK levels were decreased, and lung cancer cell growth was subsequently suppressed. This study reveals the intriguing role and molecular mechanism of HDAC6 as a tumor promoter, and its inhibition represents a promising approach for anticancer therapy.
Community acceptability, participation, and adherence to mass drug administration with primaquine for Plasmodium vivax elimination in Southern Thailand: a mixed methods approach
Authors: Saita Sayambhu , Roobsoong Wanlapa , Khammaneechan Patthanasak , Sukchan Phnom , Lawpoolsri Saranath , Sattabongkot Jetsumon , Cui Liwang , Okanurak Kamolnetr , Phuanukoonnon Suparat , Parker Daniel M. 
Published: January 2023

Abstract
Background
Mass drug administration (MDA) with primaquine (PQ) is being considered for accelerating Plasmodium vivax elimination in remaining active foci. This study aimed to determine the acceptability of MDA with PQ in malaria endemic villages in a malarious setting in the South of Thailand undergoing MDA with PQ.

Methods
A cross-sectional mixed-methods approach was conducted in seven malaria endemic villages where MDA with PQ was implemented. The data were collected from community villagers and health workers using structured questionnaires, in-depth interviews, and focus group discussions. Descriptive statistics and logistic regression models were used for quantitative data analysis. Thematic analysis was applied for qualitative data.

Results
Among a total of 469 participants from the MDA villages, 293 participants were eligible for MDA with PQ and 79.86% (234) completed 14-days of PQ. The logistic regressions indicated that males (adjusted odds ratio: 2.52 [95% confidence interval: 1.33–4.81]) and those who are farmers (2.57 [1.12–5.90]) were most likely to participate in the MDA. Among 293 participants in the post-MDA study, 74.06% had originally agreed to participate in the MDA with PQ while 25.94% had originally reported not wanting to participate in the MDA. Of those who originally reported being willing to participate in the MDA, 71.23% followed through with participation in the first or second round. Conversely, 93.24% of those who originally reported not being willing to participate in the MDA did in fact participate in the MDA. Factors contributing to higher odds of agreeing to participate and following through with participation included being male (1.98 [1.06–3.69]) and correctly responding that malaria is preventable (2.32 [1.01–5.35]) with some differences by village. Five key themes emerged from the qualitative analyses: concern about side effects from taking PQ; disbelief that malaria could be eliminated in this setting; low overall concern about malaria infections; misunderstandings about malaria; and a general need to tailor public health efforts for this unique context.

Conclusion
While the reported likelihood of participating in MDA was high in this setting, actual follow-through was relatively moderate, partially because of eligibility (roughly 71% of those in the follow-up survey who originally agreed to participate actually followed through with participation). One of the largest concerns among study participants was PQ-related side effects—and these concerns likely heavily influenced participant adherence to the MDA. The results of this study can be used to tailor future MDAs, or other public health interventions, in this and potentially other similar settings.
Peptide-anchored neutrophil membrane-coated biomimetic nanodrug for targeted treatment of rheumatoid arthritis
Authors: Yang Ni , Li Miaomiao , Wu Ling , Song Yinhong , Yu Shi , Wan Yingying , Cheng Wenjing , Yang Baoye , Mou Xiaoqin , Yu Hong , Zheng Jing , Li Xinzhi , Yu Xiang 
Published: January 2023

AbstractMacrophage polarization determines the production of cytokines that fuel the initiation and evolution of rheumatoid arthritis (RA). Thus, modulation of macrophage polarization might represent a potential therapeutic strategy for RA. However, coordinated modulation of macrophages in the synovium and synovial fluid has not been achieved thus far. Herein, we develop a biomimetic ApoA-I mimetic peptide-modified neutrophil membrane-wrapped F127 polymer (R4F-NM@F127) for targeted drug delivery during RA treatment. Due to the high expression of adhesion molecules and chemokine receptors on neutrophils, the neutrophil membrane coating can endow the nanocarrier with synovitis-targeting ability, with subsequent recruitment to the synovial fluid under the chemotactic effects of IL-8. Moreover, R4F peptide modification further endows the nanocarrier with the ability to target the SR-B1 receptor, which is highly expressed on macrophages in the synovium and synovial fluid. Long-term in vivo imaging shows that R4F-NM@F127 preferentially accumulates in inflamed joints and is engulfed by macrophages. After loading of the anti-inflammatory drug celastrol (Cel), R4F-NM@F127-Cel shows a significant reduction in hepatotoxicity, and effectively inhibits synovial inflammation and alleviates joint damage by reprogramming macrophage polarization. Thus, our results highlight the potential of the coordinated targeted modulation of macrophages as a promising therapeutic option for the treatment of RA.
Implementing electronic patient reported outcomes in inflammatory bowel disease: patient participation, score reliability and validity
Authors: Deutscher Daniel , Weil Clara , Chodick Gabriel , Tsukinovsky Sveta , Bodger Keith , Waterman Matti , Kariv Revital 
Published: January 2023

Abstract
Background
Patient-reported outcome measures (PROMs) are recommended for assessing patient-centered outcomes in inflammatory bowel disease (IBD). The main aims were to assess the level of participation in an electronic PROM (ePROM) data collection system among patients with IBD, and evaluate reliability and validity of the resulting scores.

Methods
Patients included in the IBD registry of Maccabi Healthcare Services, a state-mandated healthcare provider for over 2.6 million people in Israel, were invited to complete the IBD-Control measure and a general health item, with follow-up ePROMs at 3 and 6 months including a global rating of change item. Descriptive statistics were used to compare patient characteristics by participation rate, and assess survey completion time. Initial scores were assessed for internal consistency reliability using Cronbach's alpha. Test–retest reliability was assessed using the intraclass correlation coefficient from paired scores of patients identified as unchanged between the initial and first follow-up. Construct validity was assessed by the ability of IBD-control scores to discriminate between patient sub-groups in expected ways. Empirical validity was assessed using ePROM score correlations with laboratory markers of disease activity. Score coverage was also assessed.

Results
A total of 13,588 patients were invited to participate [Mean age = 49 years (SD = 17); females = 51%]. Participation rate was 31.5%. Participants compared to non-participants were slightly older, were more likely to be female, to have a history of biologic treatment, to have higher socio-economic status, and to be more experienced in the usage of the digital patient portal. Median survey completion time was approximately 1:30 min. Internal consistency and test–retest reliability were 0.86 and 0.98, respectively. Scores discriminated between patient sub-groups in clinically expected ways, with expected correlations to laboratory markers of disease activity. A notable ceiling effect was observed (> 15%) for IBD-Control scores.

Conclusions
Feasibility, reliability, and validity of the ePROM system was supported for measuring the level of perceived disease control in patients diagnosed with IBD in Israel. Additional research is needed to identify ways to increase patient participation, assess clinical implications of the identified measurement ceiling of the IBD-control, and evaluate the added value of the derived scores in support of clinical decision making.
Therapeutic benefits of lower limb prostheses: a systematic review
Authors: Lathouwers Elke , Díaz María Alejandra , Maricot Alexandre , Tassignon Bruno , Cherelle Claire , Cherelle Pierre , Meeusen Romain , De Pauw Kevin 
Published: January 2023

Abstract
Background
Enhancing the quality of life of people with a lower limb amputation is critical in prosthetic development and rehabilitation. Yet, no overview is available concerning the impact of passive, quasi-passive and active ankle–foot prostheses on quality of life.

Objective
To systematically review the therapeutic benefits of performing daily activities with passive, quasi-passive and active ankle–foot prostheses in people with a lower limb amputation.

Methods
We searched the Pubmed, Web of Science, Scopus and Pedro databases, and backward citations until November 3, 2021. Only English-written randomised controlled trials, cross-sectional, cross-over and cohort studies were included when the population comprised individuals with a unilateral transfemoral or transtibial amputation, wearing passive, quasi-passive or active ankle–foot prostheses. The intervention and outcome measures had to include any aspect of quality of life assessed while performing daily activities. We synthesised the participants’ characteristics, type of prosthesis, intervention, outcome and main results, and conducted risk of bias assessment using the Cochrane risk of bias tool. This study is registered on PROSPERO, number CRD42021290189.

Results
We identified 4281 records and included 34 studies in total. Results indicate that quasi-passive and active prostheses are favoured over passive prostheses based on biomechanical, physiological, performance and subjective measures in the short-term. All studies had a moderate or high risk of bias.

Conclusion
Compared to passive ankle–foot prostheses, quasi-passive and active prostheses significantly enhance the quality of life. Future research should investigate the long-term therapeutic benefits of prosthetics devices.