bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting RNA N6-methyladenosine to synergize with immune checkpoint therapy
Authors: Zhou Xianyong , Li Chen , Chen Tong , Li Wenhao , Wang Xiaolong , Yang Qifeng 
Published: February 2023

AbstractCancer immunotherapy, especially immune checkpoint therapy, has revolutionized therapeutic options by reactivating the host immune system. However, the efficacy varies, and only a small portion of patients develop sustained antitumor responses. Hence, illustrating novel strategies that improve the clinical outcome of immune checkpoint therapy is urgently needed. N6-methyladenosine (m6A) has been proved to be an efficient and dynamic posttranscriptional modification process. It is involved in numerous RNA processing, such as splicing, trafficking, translation and degradation. Compelling evidence emphasizes the paramount role of m6A modification in the regulation of immune response. These findings may provide a foundation for the rational combination of targeting m6A modification and immune checkpoints in cancer treatment. In the present review, we summarize the current landscape of m6A modification in RNA biology, and highlight the latest findings on the complex mechanisms by which m6A modification governs immune checkpoint molecules. Furthermore, given the critical role of m6A modification in antitumor immunity, we discuss the clinical significance of targeting m6A modification to improve the efficacy of immune checkpoint therapy for cancer control.
Cross-talk between cancer stem cells and immune cells: potential therapeutic targets in the tumor immune microenvironment
Authors: Wu Bo , Shi Xiang , Jiang Meixi , Liu Hongxu 
Published: February 2023

AbstractOngoing research has revealed that the existence of cancer stem cells (CSCs) is one of the biggest obstacles in the current cancer therapy. CSCs make an influential function in tumor progression, recurrence and chemoresistance due to their typical stemness characteristics. CSCs are preferentially distributed in niches, and those niche sites exhibit characteristics typical of the tumor microenvironment (TME). The complex interactions between CSCs and TME illustrate these synergistic effects. The phenotypic heterogeneity within CSCs and the spatial interactions with the surrounding tumor microenvironment led to increased therapeutic challenges. CSCs interact with immune cells to protect themselves against immune clearance by exploiting the immunosuppressive function of multiple immune checkpoint molecules. CSCs also can protect themselves against immune surveillance by excreting extracellular vesicles (EVs), growth factors, metabolites and cytokines into the TME, thereby modulating the composition of the TME. Therefore, these interactions are also being considered for the therapeutic development of anti-tumor agents. We discuss here the immune molecular mechanisms of CSCs and comprehensively review the interplay between CSCs and the immune system. Thus, studies on this topic seem to provide novel ideas for reinvigorating therapeutic approaches to cancer.
Local delivery of gaseous signaling molecules for orthopedic disease therapy
Authors: Sun Jiaxuan , Wang Wenzhi , Hu Xianli , Zhang Xianzuo , Zhu Chen , Hu Jinming , Ma Ruixiang 
Published: February 2023

AbstractOver the past decade, a proliferation of research has used nanoparticles to deliver gaseous signaling molecules for medical purposes. The discovery and revelation of the role of gaseous signaling molecules have been accompanied by nanoparticle therapies for their local delivery. While most of them have been applied in oncology, recent advances have demonstrated their considerable potential in diagnosing and treating orthopedic diseases. Three of the currently recognized gaseous signaling molecules, nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S), are highlighted in this review along with their distinctive biological functions and roles in orthopedic diseases. Moreover, this review summarizes the progress in therapeutic development over the past ten years with a deeper discussion of unresolved issues and potential clinical applications.
Combining robot-assisted therapy with virtual reality or using it alone? A systematic review on health-related quality of life in neurological patients
Authors: Zanatta Francesco , Farhane-Medina Naima Z. , Adorni Roberta , Steca Patrizia , Giardini Anna , D’Addario Marco , Pierobon Antonia 
Published: February 2023

Abstract
Background
In the field of neurorehabilitation, robot-assisted therapy (RAT) and virtual reality (VR) have so far shown promising evidence on multiple motor and functional outcomes. The related effectiveness on patients’ health-related quality of life (HRQoL) has been investigated across neurological populations but still remains unclear. The present study aimed to systematically review the studies investigating the effects of RAT alone and with VR on HRQoL in patients with different neurological diseases.

Methods
A systematic review of the studies evaluating the impact of RAT alone and combined with VR on HRQoL in patients affected by neurological diseases (i.e., stroke, multiple sclerosis, spinal cord injury, Parkinson’s Disease) was conducted according to PRISMA guidelines. Electronic searches of PubMed, Web of Science, Cochrane Library, CINAHL, Embase, and PsychINFO (2000–2022) were performed. Risk of bias was evaluated through the National Institute of Health Quality Assessment Tool. Descriptive data regarding the study design, participants, intervention, rehabilitation outcomes, robotic device typology, HRQoL measures, non-motor factors concurrently investigated, and main results were extracted and meta-synthetized.

Results
The searches identified 3025 studies, of which 70 met the inclusion criteria. An overall heterogeneous configuration was found regarding the study design adopted, intervention procedures and technological devices implemented, rehabilitation outcomes (i.e., related to both upper and lower limb impairment), HRQoL measures administered, and main evidence. Most of the studies reported significant effects of both RAT and RAT plus VR on patients HRQoL, whether they adopted generic or disease-specific HRQoL measures. Significant post-intervention within-group changes were mainly found across neurological populations, while fewer studies reported significant between-group comparisons, and then, mostly in patients with stroke. Longitudinal investigations were also observed (up to 36 months), but significant longitudinal effects were exclusively found in patients with stroke or multiple sclerosis. Finally, concurrent evaluations on non-motor outcomes beside HRQoL included cognitive (i.e., memory, attention, executive functions) and psychological (i.e., mood, satisfaction with the treatment, device usability, fear of falling, motivation, self-efficacy, coping, and well-being) variables.

Conclusions
Despite the heterogeneity observed among the studies included, promising evidence was found on the effectiveness of RAT and RAT plus VR on HRQoL. However, further targeted short- and long-term investigations, are strongly recommended for specific HRQoL subcomponents and neurological populations, through the adoption of defined intervention procedures and disease-specific assessment methodology.
Factors associated with health-related quality of life in people living with HIV in Norway
Authors: Skogen Vegard , Rohde Gudrun E. , Langseth Ranveig , Rysstad Ole , Sørlie Tore , Lie Birgit 
Published: February 2023

Abstract
Background
Despite the advances in the treatment of HIV, people living with HIV (PLHIV) still experience impairment of health-related quality of life (HRQOL). The aim of the study was to explore factors associated with HRQOL in a well-treated Norwegian HIV population.

Methods
Two hundred and forty-five patients were recruited from two outpatient clinics to participate in this cross-sectional study of addiction, mental distress, post-traumatic stress disorder, fatigue, somatic health, and HRQOL. The latter was measured using the 36-Item Short Form Health Survey (SF-36). Stepwise multiple linear regression analysis was used to examine the adjusted associations between demographic and disease-related variables and HRQOL.

Results
The study population was virologically and immunologically stable. Their mean age was 43.8 (SD = 11.7) years, 131 (54%) were men, and 33% were native Norwegians. Compared with the general population (published in previous studies), patients reported worse SF-36 scores for five of eight domains: mental health, general health, social function, physical role limitation, and emotional role limitation (all p < 0.001). Compared with men, women reported better SF-36 scores within the domains vitality (63.1 (23.6) vs. 55.9 (26.7), p = 0.026) and general health (73.4 (23.2) vs. 64.4 (30.1), p = 0.009). In the multivariate analyses, higher SF-36- physical component score values were independently associated with young age (p = 0.020), being employed, student, or pensioner (p = 0.009), low comorbidity score (p = 0.015), low anxiety and depression score (p = 0.015), being at risk of drug abuse (p = 0.037), and not being fatigued (p < 0.001). Higher SF-36-mental component score values were independently associated with older age (p = 0.018), being from a country outside Europe or from Norway (p = 0.029), shorter time since diagnosis, low anxiety and depression score (p < 0.001), answering ‘no’ regarding alcohol abuse (p = 0.013), and not being fatigued (p < 0.001).

Conclusions
HRQOL was poorer in PLHIV than in the general population in Norway. It is important to focus on somatic and mental comorbidities when delivering health-care services in the ageing population of PLHIV to improve HRQOL even among a well-treated group of PLHIV as found in Norway.
Additive prognostic value of serum calcium to the ESC risk stratification in patients with acute pulmonary embolism
Authors: Zhang Jiarui , Ali Adila , Liu Yu , Peng Lige , Pu Jiaqi , Yi Qun , Zhou Haixia 
Published: February 2023

Abstract
Background
Hypocalcemia has been shown to be involved in the adverse outcomes of acute pulmonary embolism (APE). We aimed to determine the incremental value of adding hypocalcemia, defined as serum calcium level ≤ 2.12 mmol/L, on top of the European Society of Cardiology (ESC) prognostic algorithm, for the prediction of in-hospital mortality in APE patients, which in turn could lead to the optimization of APE management.

Methods
This study was conducted at West China Hospital of Sichuan University from January 2016 to December 2019. Patients with APE were retrospectively analyzed and divided into 2 groups based on serum calcium levels. Associations between hypocalcemia and adverse outcomes were assessed by Cox analysis. The accuracy of risk stratification for in-hospital mortality was assessed with the addition of serum calcium to the current ESC prognostic algorithm.

Results
Among 803 patients diagnosed with APE, 338 (42.1%) patients had serum calcium levels ≤ 2.12 mmol/L. Hypocalcemia was significantly associated with higher in-hospital and 2-year all-cause mortality compared to the control group. The addition of serum calcium to ESC risk stratification enhanced net reclassification improvement. Low-risk group with serum calcium level > 2.12 mmol/L had a 0% mortality rate, improving the negative predictive value up to 100%, while high-risk group with serum calcium level ≤ 2.12 mmol/L indicated a higher mortality of 25%.

Conclusion
Our study identified serum calcium as a novel predictor of mortality in patients with APE. In the future, serum calcium may be added to the commonly used ESC prognostic algorithm for better risk stratification of patients suffering from APE.
Characterization of the intestinal fungal microbiome in patients with hepatocellular carcinoma
Authors: Zhang Lilong , Chen Chen , Chai Dongqi , Li Chunlei , Qiu Zhendong , Kuang Tianrui , Liu Li , Deng Wenhong , Wang Weixing 
Published: February 2023

Abstract
Objective
Gut mycobiota plays a crucial role in benign liver diseases; however, its correlation with hepatocellular carcinoma (HCC) remains elusive. This study aimed to elucidate fungal differences in patients with HCC-associated cirrhosis compared to cirrhotic patients without HCC and healthy controls.

Methods
The 72 fecal samples from 34 HCC patients, 20 cirrhotic patients, and 18 healthy controls were collected and analyzed using ITS2 rDNA sequencing.

Results
Our results revealed the presence of intestinal fungal dysbiosis with significant enrichment of opportunistic pathogenic fungi such as Malassezia, Malassezia sp., Candida, and C. albicans in HCC patients compared with healthy controls and cirrhosis patients. Alpha-diversity analysis demonstrated that patients with HCC and cirrhosis showed decreased fungal diversity compared to healthy controls. Beta diversity analysis indicated that the three groups exhibited significant segregated clustering. Besides, C. albicans was found to be significantly more abundant in the HCC patients with TNM stage III-IV than those with stage I-II, in contrast to the commensal organism S. cerevisiae. We also confirmed that the HCC patients were successfully classified with an area under the curve value of 0.906 based on the fecal fungal signature. Finally, our animal experiments confirm that aberrant colonization of the intestine by C. albicans and M. furfur can promote the development of HCC.

Conclusions
This study indicates that dysbiosis of the gut mycobiome might be involved in HCC development.
Trial registration: ChiCTR, ChiCTR2100054537. Registered 19 December 2021, http://www.chictr.org.cn/edit.aspx?pid=144550&htm=4
The multi-grip and standard myoelectric hand prosthesis compared: does the multi-grip hand live up to its promise?
Authors: Kerver Nienke , Schuurmans Verena , van der Sluis Corry K. , Bongers Raoul M. 
Published: February 2023

Abstract
Background
Multi-grip myoelectric hand prostheses (MHPs), with five movable and jointed fingers, have been developed to increase functionality. However, literature comparing MHPs with standard myoelectric hand prostheses (SHPs) is limited and inconclusive. To establish whether MHPs increase functionality, we compared MHPs with SHPs on all categories of the International Classification of Functioning, Disability, and Health-model (ICF-model).

Methods
MHP users (N = 14, 64.3% male, mean age = 48.6 years) performed physical measurements (i.e., Refined Clothespin Relocation Test (RCRT), Tray-test, Box and Blocks Test, Southampton Hand Assessment Procedure) with their MHP and an SHP to compare the joint angle coordination and functionality related to the ICF-categories ‘Body Function’ and ‘Activities’ (within-group comparisons). SHP users (N = 19, 68.4% male, mean age = 58.1 years) and MHP users completed questionnaires/scales (i.e., Orthotics and Prosthetics Users’ Survey—The Upper Extremity Functional Status Survey /OPUS–UEFS, Trinity Amputation and Prosthesis Experience Scales for upper extremity/TAPES-Upper, Research and Development-36/RAND-36, EQ-5D-5L, visual analogue scale/VAS, the Dutch version of the Quebec User Evaluation of Satisfaction with assistive technology/D-Quest, patient-reported outcome measure to assess the preferred usage features of upper limb prostheses/PUF-ULP) to compare user experiences and quality of life in the ICF-categories ‘Activities’, ‘Participation’, and ‘Environmental Factors’ (between-group comparisons).

Results
‘Body Function’ and ‘Activities’: nearly all users of MHPs had similar joint angle coordination patterns with an MHP as when they used an SHP. The RCRT in the upward direction was performed slower in the MHP condition compared to the SHP condition. No other differences in functionality were found. ‘Participation’: MHP users had a lower EQ-5D-5L utility score; experienced more pain or limitations due to pain (i.e., measured with the RAND-36). ‘Environmental Factors’: MHPs scored better than SHPs on the VAS-item holding/shaking hands. The SHP scored better than the MHP on five VAS-items (i.e., noise, grip force, vulnerability, putting clothes on, physical effort to control) and the PUF-ULP.

Conclusion
MHPs did not show relevant differences in outcomes compared to SHPs on any of the ICF-categories. This underlines the importance of carefully considering whether the MHP is the most suitable option for an individual taking into account the additional costs of MHPs.
MiR-218-5p-dependent SOCS3 downregulation increases osteoblast differentiation inpostmenopausal osteoporosis
Authors: Zhou Qian , Zhou Lihua , Li Jun 
Published: February 2023

Abstract
Background
Postmenopausal osteoporosis (POP) is a prevalent skeletal disease among elderly women. Previous study indicated that suppressor of cytokine signaling 3 (SOCS3) participates in the regulation of bone marrow stromal cell (BMSC) osteogenesis. Here, we further investigated the exact function and mechanism of SOCS3 in POP progression.

Methods
BMSCs were isolated from Sprague–Dawley rats and treated with Dexamethasone (Dex). Alizarin Red staining and ALP activity assays were applied to assess the osteogenic differentiation of rat BMSCs under the indicated conditions. Osteogenic genes (ALP, OPN, OCN, COL1) mRNA levels were determined using quantitative RT-PCR. Luciferase reporter assay verified the interaction between SOCS3 and miR-218-5p. Rat models of POP were established in ovariectomized (OVX) rats to detect the in vivo effects of SOCS3 and miR-218-5p.

Results
We found that silencing SOCS3 antagonized the suppressive effects of Dex on the osteogenic differentiation of BMSCs. SOCS3 was found to be targeted by miR-218-5p in BMSCs. The SOCS3 levels were negatively modulated by miR-218-5p in femurs of POP rats. MiR-218-5p upregulation promoted the BMSC osteogenic differentiation, while SOCS3 overexpression reversed the effects of miR-218-5p. Moreover, SOCS3 was highly expressed and miR-218-5p was downregulated in the OVX rat models, and silencing SOCS3 or overexpressing miR-218-5p alleviated POP in OVX rats by promoting osteogenesis.

Conclusion
SOCS3 downregulation mediated by miR-218-5p increases osteoblast differentiation to alleviate POP.
Left atrial dissection after a supra-annular mitral valve replacement for endocarditis
Authors: de Villiers de la Noue Valentin , Théry Guillaume , Faroux Laurent , Belkessa Nasreddine , Rubin Sylvain , Mourvillier Bruno , Goury Antoine 
Published: February 2023

Abstract
Background
Left atrial dissection is a rare and a potentially fatal complication of cardiac surgery. Multi-modal imagery is helpful for the diagnosis and to guide the treatment.

Case presentation
We report the case of a 66-year-old female patient who underwent a combined mitral and aortic valve replacement for degenerative valvular disease. She presented an infectious endocarditis revealed by a third-degree atrioventricular bloc and had a redo mitral- and aortic valve replacement. Mitral valve was inserted in supra-annular position due to annular destruction. Post-operative course was marked by a refractory acute heart failure explained by a left atrial wall dissection confirmed by transoesophageal echocardiography and synchronized cardiac CT-scan. Surgical treatment was theoretically indicated but considering the high risk of a third surgery, a palliative care support was collegially decided.

Conclusions
Left atrial dissection can occur after a redo surgery and supra-annular mitral valve implantation. Multi-modal imagery including transoesophageal echocardiography and cardiac CT-scan is helpful for the diagnosis.
Postoperative clinical outcomes of patients with thymic epithelial tumors after over-3-year follow-up at a single-center
Authors: Jiao Peng , Tian Wen-Xin , Wu Fan-Juan , Liu Yu-Xing , Wu Jiang-Yu , Sun Yao-Guang , Yu Han-Bo , Huang Chuan , Wu Qing-Jun , Ma Chao , Li Dong-Hang , Tong Hong-Feng , Li Jun 
Published: February 2023

Abstract
Background
To evaluate postoperative clinical outcomes and analyze influencing factors for patients with thymic epithelial tumors over 3 years after operation.

Methods
Patients with thymic epithelial tumors (TETs) who underwent surgical treatment in the Department of Thoracic Surgery at Beijing Hospital from January 2011 to May 2019 were retrospectively enrolled in the study. Basic patient information, clinical, pathological, and perioperative data were collected. Patients were followed up by telephone interviews and outpatient records. Statistical analyses were performed using SPSS version 26.0.

Results
A total of 242 patients (129 men, 113 women) with TETs were included in this study, of which 150 patients (62.0%) were combined with myasthenia gravis (MG) and 92 patients (38.0%) were not. 216 patients were successfully followed up and their complete information was available. The median follow-up period was 70.5 months (range, 2–137 months). The 3-year overall survival (OS) rate of the whole group was 93.9%, and the 5-year OS rate was 91.1%. The 3-year relapse-free survival (RFS) rate of the whole group was 92.2%, and the 5-year relapse-free survival rate was 89.8%. Multivariable COX regression analysis indicated that recurrence of thymoma was an independent risk factor for OS. Younger age, Masaoka-Koga stage III + IV, and TNM stage III + IV were independent risk factors for RFS. Multivariable COX regression analysis indicated that Masaoka-Koga staging III + IV, WHO type B + C were independent risk factors for postoperative improvement of MG. For patients with MG, the postoperative complete stable remission (CSR) rate was 30.5%. And the result of multivariable COX regression analysis showed that thymoma patients with MG with Osserman staging IIA + IIB + III + IV were not prone to achieving CSR. Compared with patients without MG, MG was more likely to develop in patients with WHO classification type B, and patients with myasthenia gravis were younger, with longer operative duration, and more likely to develop perioperative complications.

Conclusions
The 5-year overall survival rate of patients with TETs was 91.1% in this study. Younger age and advanced stage were independent risk factors for RFS of patients with TETs, and recurrence of thymoma were independent risk factors for OS. In patients with MG, WHO classification type B and advanced stage were independent predictors of poor outcomes of MG treatment after thymectomy.