bluuebunny/crossref_metadata_2025_split huggingface dataset:
How to adopt technologies in home care: a mixed methods study on user experiences and change of home care in Finland
Authors: Anttila Minna , Koivisto Juha , Luoma Minna-Liisa , Anttila Heidi 
Published: December 2023

Abstract
Background
There is a need for better adoption of technology to meet the needs of home care professionals, older people, and informal caregivers.

Methods
Mixed methods were used to describe and analyse quantitative and qualitative data in a Finnish governmental programme called KATI. The study was three-fold: it 1) listed what kinds of technologies were piloted and deployed in a national study, 2) provided information from the perspectives of home care professionals about requirements to use technology by using focus-group interviews, and 3) assessed experiences of how the adoption of technology changes work and work processes over time by using repeated surveys. Informants in interviews (n = 25) and surveys (n = 90) were home care professionals, who also described the perspectives of older people and informal caregivers. The conceptual models framing the study were adapted from the Technology Acceptance Model and DirVA PROVE-IT.

Results
There were 80 technology pilots, in which variety of technologies were followed in home care. Familiarity with, commitment to and understanding of technology benefits were considered to be requirements for the technology to be used. The adoption of technology provided new skills and information about older people’s wellbeing, realisation of treatment and new possibilities in home care. It developed new procedures to focus on older people’s needs and motivated professionals by gained concrete aid. It enabled them to leave out some concrete procedures as unnecessary. On the other hand, there were also pessimistic and negative experiences when technology use provided nothing new or did not change anything.

Conclusions
The adoption of technology is dependent on the technology and its integration into the prevailing service practice. When they both work, it is possible to leave out unnecessary procedures in care, allocate resources and save time. It is possible to be aware of older people’s safety and how they cope at home, find new ways to get involved in older people’s lives, gain insight, and make changes at work. Continuous on-site training, modifications in service practices and communication throughout organisations is needed.
Circular RNA circEYA3 promotes the radiation resistance of hepatocellular carcinoma via the IGF2BP2/DTX3L axis
Authors: Hu Pan , Lin Letao , Huang Tao , Li Zhenyu , Xiao Meigui , Guo Huanqing , Chen Guanyu , Liu Dengyao , Ke Miaola , Shan Hongbo , Zhang Fujun , Zhang Yanling 
Published: December 2023

Abstract
Background
Hepatocellular carcinoma (HCC) has a high incidence and mortality rate despite various treatment options, including 125I seed implantation. However, recurrence and radiation resistance remain challenging issues. Hsa_circ_0007895 (circEYA3)—derived from exons 2–6 of EYA3–facilitates the proliferation and progression of pancreatic ductal adenocarcinoma. However, the role of circEYA3 in HCC 125I radiation resistance remains unclear. Thus, we aimed to investigate the functions and underlying molecular mechanisms of circEYA3 in HCC under 125I and X-ray irradiation conditions.

Methods
CircEYA3 was identified by RNA-seq in patients with HCC before and after 125I seed implantation treatment, followed by fluorescence in situ hybridization and RNase R assays. The radiosensitivity of HCC cell lines irradiated with 125I seeds or external irradiation were evaluated using the Cell Counting Kit 8, flow cytometry, γH2A.X immunofluorescence and comet assays. RNA pull-down and RNA immunoprecipitation assays were performed to explore the interactions between circEYA3 and IGF2BP2. DTX3L mRNA was identified by RNA-seq in PLC/PRF/5 cells with overexpressed circEYA3. The corresponding in vitro results were verified using a mouse xenograft model.

Results
CircEYA3 decreased the radiosensitivity of HCC cells both in vitro and in vivo. Notably, using a circRNA pulldown assay and RNA-binding protein immunoprecipitation, we identified IGF2BP2 as a novel and robust interacting protein of circEYA3. Mechanistically, circEYA3 binds to IGF2BP2 and enhances its ability to stabilize DTX3L mRNA, thereby specifically alleviating radiation-induced DNA damage in HCC cells.

Conclusions
Our findings demonstrate that circEYA3 increases the radioresistance of HCC to 125I seeds and external irradiation via the IGF2BP2/DTX3L axis. Thus, circEYA3 might be a predictive indicator and intervention option for 125I brachytherapy or external radiotherapy in HCC.
Targeting MHC-I molecules for cancer: function, mechanism, and therapeutic prospects
Authors: Wu Xiangyu , Li Tianhang , Jiang Rui , Yang Xin , Guo Hongqian , Yang Rong 
Published: December 2023

AbstractThe molecules of Major histocompatibility class I (MHC-I) load peptides and present them on the cell surface, which provided the immune system with the signal to detect and eliminate the infected or cancerous cells. In the context of cancer, owing to the crucial immune-regulatory roles played by MHC-I molecules, the abnormal modulation of MHC-I expression and function could be hijacked by tumor cells to escape the immune surveillance and attack, thereby promoting tumoral progression and impairing the efficacy of cancer immunotherapy. Here we reviewed and discussed the recent studies and discoveries related to the MHC-I molecules and their multidirectional functions in the development of cancer, mainly focusing on the interactions between MHC-I and the multiple participators in the tumor microenvironment and highlighting the significance of targeting MHC-I for optimizing the efficacy of cancer immunotherapy and a deeper understanding of the dynamic nature and functioning mechanism of MHC-I in cancer.
Discovery of a novel lipid metabolism-related gene signature to predict outcomes and the tumor immune microenvironment in gastric cancer by integrated analysis of single-cell and bulk RNA sequencing
Authors: Zhang Jinze , Wang He , Tian Yu , Li Tianfeng , Zhang Wei , Ma Li , Chen Xiangjuan , Wei Yushan 
Published: December 2023

AbstractGastric cancer (GC) is a pressing global clinical issue, with few treatment options and a poor prognosis. The onset and spread of stomach cancer are significantly influenced by changes in lipid metabolism-related pathways. This study aimed to discover a predictive signature for GC using lipid metabolism-related genes (LMRGs) and examine its correlation with the tumor immune microenvironment (TIME). Transcriptome data and clinical information from patients with GC were collected from the TCGA and GEO databases. Data from GC samples were analyzed using both bulk RNA-seq and single-cell sequencing of RNA (scRNA-seq). To identify survival-related differentially expressed LMRGs (DE-LMRGs), differential expression and prognosis studies were carried out. We built a predictive signature using LASSO regression and tested it on the TCGA and GSE84437 datasets. In addition, the correlation of the prognostic signature with the TIME was comprehensively analyzed. In this study, we identified 258 DE-LMRGs in GC and further screened seven survival-related DE-LMRGs. The results of scRNA-seq identified 688 differentially expressed genes (DEGs) between the three branches. Two critical genes (GPX3 and NNMT) were identified using the above two gene groups. In addition, a predictive risk score that relies on GPX3 and NNMT was developed. Survival studies in both the TCGA and GEO datasets revealed that patients categorized to be at low danger had a significantly greater prognosis than those identified to be at high danger. Additionally, by employing calibration plots based on TCGA data, the study demonstrated the substantial predictive capacity of a prognostic nomogram, which incorporated a risk score along with various clinical factors. Within the high-risk group, there was a noticeable abundance of active natural killer (NK) cells, quiescent monocytes, macrophages, mast cells, and activated CD4 + T cells. In summary, a two-gene signature and a predictive nomogram have been developed, offering accurate prognostic predictions for general survival in GC patients. These findings have the potential to assist healthcare professionals in making informed medical decisions and providing personalized treatment approaches.
Ropivacaine-loaded hydrogels for prolonged relief of chemotherapy-induced peripheral neuropathic pain and potentiated chemotherapy
Authors: Qing Xin , Dou Renbin , Wang Peng , Zhou Mengni , Cao Chenchen , Zhang Huiwen , Qiu Gaolin , Yang Zhilai , Zhang Jiqian , Liu Hu , Zhu Shasha , Liu Xuesheng 
Published: December 2023

AbstractChemotherapy can cause severe pain for patients, but there are currently no satisfactory methods of pain relief. Enhancing the efficacy of chemotherapy to reduce the side effects of high-dose chemotherapeutic drugs remains a major challenge. Moreover, the treatment of chemotherapy-induced peripheral neuropathic pain (CIPNP) is separate from chemotherapy in the clinical setting, causing inconvenience to cancer patients. In view of the many obstacles mentioned above, we developed a strategy to incorporate local anesthetic (LA) into a cisplatin-loaded PF127 hydrogel for painless potentiated chemotherapy. We found that multiple administrations of cisplatin-loaded PF127 hydrogels (PFC) evoked severe CIPNP, which correlated with increased pERK-positive neurons in the dorsal root ganglion (DRG). However, incorporating ropivacaine into the PFC relieved PFC-induced CIPNP for more than ten hours and decreased the number of pERK-positive neurons in the DRG. Moreover, incorporating ropivacaine into the PFC for chemotherapy is found to upregulate major histocompatibility complex class I (MHC-I) expression in tumor cells and promote the infiltration of cytotoxic T lymphocytes (CD8+ T cells) in tumors, thereby potentiating chemotherapy efficacy. This study proposes that LA can be used as an immunemodulator to enhance the effectiveness of chemotherapy, providing new ideas for painless cancer treatment.
Examining the benefit of a higher maintenance dose of extended-release buprenorphine in opioid-injecting participants treated for opioid use disorder
Authors: Greenwald Mark K. , Wiest Katharina L. , Haight Barbara R. , Laffont Celine M. , Zhao Yue 
Published: December 2023

Abstract
Background
BUP-XR (SUBLOCADE®) is the first buprenorphine extended-release subcutaneous injection approved in the USA for monthly treatment of moderate-to-severe opioid use disorder (OUD). Among patients with OUD, those who inject or use high doses of opioids likely require higher doses of buprenorphine to maximize treatment efficacy. The objective of this analysis was to compare the efficacy and safety of 100-mg versus 300-mg maintenance doses of BUP-XR in OUD patients who inject opioids.

Methods
This was a secondary analysis of a randomized, double-blind, placebo-controlled study in which adults with moderate or severe OUD received monthly injections of BUP-XR (2 × 300-mg doses, then 4 × 100-mg or 300-mg maintenance doses) or placebo for 24 weeks. Abstinence was defined as opioid-negative urine drug screens combined with negative self-reports collected weekly. Each participant’s percentage abstinence was calculated after the first, second, and third maintenance doses in opioid-injecting and non-injecting participants. The proportion of participants achieving opioid abstinence in each group was also calculated weekly. Treatment retention rate following the first maintenance dose was estimated for opioid-injecting participants with Kaplan–Meier method. Risk-adjusted comparisons were made via inverse propensity weighting using propensity scores. Buprenorphine plasma concentration–time profiles were compared between injecting and non-injecting participants. The percentages of participants reporting treatment-emergent adverse events were compared between maintenance dose groups within injecting and non-injecting participants separately.

Results
BUP-XR 100-mg and 300-mg maintenance doses were equally effective in non-injecting participants. However, in opioid-injecting participants, the 300-mg maintenance dose delivered clinically meaningful improvements over the 100-mg maintenance dose for treatment retention and opioid abstinence. Exposure–response analyses confirmed that injecting participants would require higher buprenorphine plasma concentrations compared to non-injecting opioid participants to achieve similar efficacy in terms of opioid abstinence. Importantly, both 100- and 300-mg maintenance doses had comparable safety profiles, including hepatic safety events.

Conclusions
These analyses show clear benefits of the 300-mg maintenance dose in injecting participants, while no additional benefit was observed in non-injecting participants relative to the 100-mg maintenance dose. This is an important finding as opioid-injecting participants represent a high-risk and difficult-to-treat population. Optimal buprenorphine dosing in this population might facilitate harm reduction by improving abstinence and treatment retention.
Trial registration: ClinicalTrials.gov, NCT02357901.
Aging gene signature of memory CD8+ T cells is associated with neurocognitive functioning in Alzheimer’s disease
Authors: Young Juan Joseph , Park Hong-Jai , Kim Minhyung , Par-Young Jennefer , Bartlett Hugh , Kim Hye Sun , Unlu Serhan , Osmani Lais , Shin Min Sun , Bucala Richard , van Dyck Christopher H. , Allore Heather , Mecca Adam P. , You Sungyong , Kang Insoo 
Published: December 2023

Abstract
Background
Memory CD8+ T cells expand with age. We previously demonstrated an age-associated expansion of effector memory (EM) CD8+ T cells expressing low levels of IL-7 receptor alpha (IL-7Rαlow) and the presence of its gene signature (i.e., IL-7Rαlow aging genes) in peripheral blood of older adults without Alzheimer’s disease (AD). Considering age as the strongest risk factor for AD and the recent finding of EM CD8+ T cell expansion, mostly IL-7Rαlow cells, in AD, we investigated whether subjects with AD have alterations in IL-7Rαlow aging gene signature, especially in relation to genes possibly associated with AD and disease severity.

Results
We identified a set of 29 candidate genes (i.e., putative AD genes) which could be differentially expressed in peripheral blood of patients with AD through the systematic search of publicly available datasets. Of the 29 putative AD genes, 9 genes (31%) were IL-7Rαlow aging genes (P < 0.001), suggesting the possible implication of IL-7Rαlow aging genes in AD. These findings were validated by RT-qPCR analysis of 40 genes, including 29 putative AD genes, additional 9 top IL-7R⍺low aging but not the putative AD genes, and 2 inflammatory control genes in peripheral blood of cognitively normal persons (CN, 38 subjects) and patients with AD (40 mild cognitive impairment and 43 dementia subjects). The RT-qPCR results showed 8 differentially expressed genes between AD and CN groups; five (62.5%) of which were top IL-7Rαlow aging genes (FGFBP2, GZMH, NUAK1, PRSS23, TGFBR3) not previously reported to be altered in AD. Unbiased clustering analysis revealed 3 clusters of dementia patients with distinct expression levels of the 40 analyzed genes, including IL-7Rαlow aging genes, which were associated with neurocognitive function as determined by MoCA, CDRsob and neuropsychological testing.

Conclusions
We report differential expression of “normal” aging genes associated with IL‐7Rαlow EM CD8+ T cells in peripheral blood of patients with AD, and the significance of such gene expression in clustering subjects with dementia due to AD into groups with different levels of cognitive functioning. These results provide a platform for studies investigating the possible implications of age-related immune changes, including those associated with CD8+ T cells, in AD.
Efficacy and safety comparison of infrared laser moxibustion and traditional moxibustion in knee osteoarthritis: study protocol for a Zelen-design randomized controlled non-inferiority clinical trial
Authors: Wang Zhong-yu , Chen Fang-fang , Li Jiang-Tao , Zhao Bai-xiao , Han Li 
Published: December 2023

Abstract
Background
Knee osteoarthritis (KOA) is the most common chronic degenerative joint disease and places a substantial burden on the public health resources in China. The purpose of this study is to preliminarily evaluate whether infrared laser moxibustion (ILM) is non-inferior to traditional moxibustion (TM) in the treatment of KOA.

Materials and methods
In the designed Zelen-design randomized controlled non-inferiority clinical trial, a total of 74 patients with KOA will be randomly allocated to one of two interventions: ILM treatment or TM treatment. All participants will receive a 6-week treatment and a follow-up 4 weeks after treatment. The primary outcomes will be the mean change in pain scores on the numeric rating scale (NRS) measured at baseline and the end of last treatment at week 6. The secondary outcomes will be the pain scores on the NRS from weeks 1 to 5 after the start of treatment and the changes from baseline to endpoints (weeks 6 and 10) in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), SF-36, knee circumference, and 6-min walking test. In addition, safety assessment will be performed throughout the trial.

Conclusion
The results of our study will help determine whether a 6-week treatment with ILM is non-inferior to TM in patients with KOA, therefore providing evidence to verify if ILM can become a safer alternative for TM in clinical applications in the future.
Trial registration: Clinical Trial Registration Platform (ChiCTR2200065264); Pre-results. Registered on 1 November 2022.
The role of Traditional Chinese medicine in anti-HBV: background, progress, and challenges
Authors: Ge Feilin , Yang Yan , Bai Zhaofang , Si Lanlan , Wang Xuemei , Yu Jia , Xiao Xiaohe , Liu Yan , Ren Zhigang 
Published: December 2023

AbstractChronic hepatitis B (CHB) remains a major world's most serious public health issues. Despite the remarkable effect of nucleos(t)ide analogues (NAs) in inhibiting hepatitis B virus (HBV) deoxyribonucleic acid (DNA) as the first-line drug, there are several limitations still, such as poor antigen inhibition, drug resistance, low-level viremia, restricting patients' functional cure. Due to the constraints of NAs, traditional medicines, such as traditional Chinese medicine (TCM), have become more prevalently used and researched in the clinical treatment of CHB as complementary alternative therapies. As a consequence, the review focuses on the background based on HBV’s life cycle as well as the NAs’ limitations, progress based on direct and indirect pathway of targeting HBV of TCM, and challenges of TCM. We found TCMs play an increasingly important role in anti-HBV. In a direct antiviral way, they regulate HBV infection, replication, assembly, and other aspects of the HBV life cycle. As for indirect way, TCMs can exert anti-HBV effects through targeting the host, including immune regulation, apoptosis, autophagy, oxidative stress, etc. Especially, TCMs have the advantages of strong antigenic inhibition compared to NAs. Specifically, we can combine the benefits of TCMs in strong HBV antigen inhibition with the benefits of NAs in targeted antiviral effects, in order to find a suitable combination of "TCM + NAs" to contribute to Chinese knowledge of the realisation of the “global elimination of HBV by 2030” goal of the World Health Organization.
Continued improvement in disease manifestations of acid sphingomyelinase deficiency for adults with up to 2 years of olipudase alfa treatment: open-label extension of the ASCEND trial
Authors: Wasserstein Melissa P. , Lachmann Robin , Hollak Carla , Barbato Antonio , Gallagher Renata C. , Giugliani Roberto , Guelbert Norberto Bernardo , Hennermann Julia B. , Ikezoe Takayuki , Lidove Olivier , Mabe Paulina , Mengel Eugen , Scarpa Maurizio , Senates Ebubekir , Tchan Michel , Villarrubia Jesus , Thurberg Beth L. , Yarramaneni Abhimanyu , Armstrong Nicole M. , Kim Yong , Kumar Monica 
Published: December 2023

Abstract
Background
Olipudase alfa is a recombinant human acid sphingomyelinase enzyme replacement therapy for non-central-nervous-system manifestations of acid sphingomyelinase deficiency (ASMD). The ASCEND randomized placebo-controlled trial in adults with ASMD demonstrated reductions in sphingomyelin storage, organomegaly, interstitial lung disease and impaired diffusion capacity of the lung (DLCO), during the first year of olipudase alfa treatment. In an ongoing open-label extension of the ASCEND trial, individuals in the placebo group crossed over to olipudase alfa, and those in the olipudase alfa group continued treatment.

Results
Thirty-five of 36 participants continued in the extension trial, and 33 completed year 2. Change-from-baseline results are presented as least-square mean percent change ± SEM. Improvements in the cross-over group after 1 year of treatment paralleled those of the olipudase alfa group from the primary analysis, while clinical improvement continued for those receiving olipudase alfa for 2 years. In the cross-over group, percent-predicted DLCO increased by 28.0 ± 6.2%, spleen volume decreased by 36.0 ± 3.0% and liver volume decreased by 30.7 ± 2.5%. For those with 2 years of olipudase alfa treatment, the percent predicted DLCO increased by 28.5 ± 6.2%, spleen volume decreased by 47.0 ± 2.7%, and liver volume decreased by 33.4 ± 2.2%. Lipid profiles and elevated liver transaminase levels improved or normalized by 1 year and remained stable through 2 years of treatment. Overall, 99% of treatment-emergent adverse events were mild or moderate, with one treatment-related serious adverse event (extrasystoles; previously documented cardiomyopathy). No individual discontinued due to an adverse event.

Conclusion
Treatment with olipudase alfa is well tolerated and reduces manifestations of chronic ASMD with sustained efficacy.
Trial registration NCT02004691 registered 9 December 2013, https://clinicaltrials.gov/ct2/show/NCT02004691