bluuebunny/crossref_metadata_2025 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

Cancer 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

Ongoing 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

Over 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

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

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

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

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

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

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

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

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.
iU-Net: a hybrid structured network with a novel feature fusion approach for medical image segmentation
Authors: Jiang Yun , Dong Jinkun , Cheng Tongtong , Zhang Yuan , Lin Xin , Liang Jing
Published: February 2023

In recent years, convolutional neural networks (CNNs) have made great achievements in the field of medical image segmentation, especially full convolutional neural networks based on U-shaped structures and skip connections. However, limited by the inherent limitations of convolution, CNNs-based methods usually exhibit limitations in modeling long-range dependencies and are unable to extract large amounts of global contextual information, which deprives neural networks of the ability to adapt to different visual modalities. In this paper, we propose our own model, which is called iU-Net bacause its structure closely resembles the combination of i and U. iU-Net is a multiple encoder-decoder structure combining Swin Transformer and CNN. We use a hierarchical Swin Transformer structure with shifted windows as the primary encoder and convolution as the secondary encoder to complement the context information extracted by the primary encoder. To sufficiently fuse the feature information extracted from multiple encoders, we design a feature fusion module (W-FFM) based on wave function representation. Besides, a three branch up sampling method(Tri-Upsample) has developed to replace the patch expand in the Swin Transformer, which can effectively avoid the Checkerboard Artifacts caused by the patch expand.

On the skin lesion region segmentation task, the segmentation performance of iU-Net is optimal, with Dice and Iou reaching 90.12% and 83.06%, respectively. To verify the generalization of iU-Net, we used the model trained on ISIC2018 dataset to test on PH2 dataset, and achieved 93.80% Dice and 88.74% IoU. On the lung feild segmentation task, the iU-Net achieved optimal results on IoU and Precision, reaching 98.54% and 94.35% respectively. Extensive experiments demonstrate the segmentation performance and generalization ability of iU-Net.
Next-generation sequencing of 500 POI patients identified novel responsible monogenic and oligogenic variants
Authors: Luo Wei , Ke Hanni , Tang Shuyan , Jiao Xue , Li Zhuqing , Zhao Shidou , Zhang Feng , Guo Ting , Qin Yingying
Published: February 2023

Background

Premature ovarian insufficiency refers to the loss of ovarian function before 40 years of age. The etiology is heterogeneous, and genetic factors account for 20–25% of cases. However, how to transform genetic findings to clinical molecular diagnose remains a challenge. To identify potential causative variations for POI, a next generation sequencing panel with 28 known causative genes of POI was designed, and a large cohort of 500 Chinese Han patients was screened directly. Pathogenic evaluation of the identified variants and the phenotype analysis were performed according to monogenic or oligogenic variants.

Results

A total of 14.4% (72/500) of the patients carried 61 pathogenic or likely pathogenic variants in 19 of the genes in the panel. Interestingly, 58 variants (95.1%, 58/61) were firstly identified in patients with POI. FOXL2 harbored the highest occurrence frequency (3.2%, 16/500), among whom presented with isolated ovarian insufficiency instead of blepharophimosis-ptosis-epicanthus inversus syndrome. Moreover, luciferase reporter assay confirmed variant p.R349G, which account for 2.6% of POI cases, impaired the transcriptional repressive effect of FOXL2 on CYP17A1. The novel compound heterozygous variants in NOBOX and MSH4 were confirmed by pedigree haplotype analysis, and digenic heterozygous variants in MSH4 and MSH5 were firstly identified. Furthermore, nine patients (1.8%, 9/500) with digenic or multigenic pathogenic variants presented with delayed menarche, early onset of POI and high prevalence of primary amenorrhea compared with those with monogenic variation(s).

Conclusions

The genetic architecture of POI has been enriched through the targeted gene panel in a large cohort of patients with POI. Specific variants in pleiotropic genes may result in isolated POI rather than syndromic POI, whereas oligogenic defects might have cumulative deleterious effects on the severity of POI phenotype.
Electronic informed consent: effects on enrolment, practical and economic benefits, challenges, and drawbacks—a systematic review of studies within randomized controlled trials
Authors: Mazzochi Ana Teresita , Dennis Martin , Chun Ho-Yan Yvonne
Published: February 2023

Background

Enrolment is one of the most challenging aspects of conducting clinical trials, preceded by the process of informed consent (IC). Different strategies to improve recruitment in clinical trials have been used, including electronic IC. During COVID-19 pandemic, barriers to enrolment have been evident. Although digital technologies were acknowledged as the future of clinical research and potential advantages were shown for recruitment, electronic informed consent (e-IC) has not yet been globally adopted. The purpose of this review is to investigate the effect of using e-IC on enrolment, practical and economic benefits, challenges, and drawbacks when compared to traditional informed consent, through a systematic review.

Methods

Embase, Global Health Library, Medline, and The Cochrane Library databases were searched. No limit was set for publication date, age, sex, or study design. We included all studies within a randomized controlled trial (RCT), published in English, Chinese or Spanish, evaluating the electronic consent process used in the parent RCT. Studies were included if any of the three components ((i) information provision, (ii) participant’s comprehension, (iii) signature) of the IC process was designed as electronic, whether administered remotely or face-to-face. The primary outcome was the rate of enrolment to the parent trial. Secondary outcomes were summarized according to the various findings reported on the use of electronic consent.

Results

From a total of 9069 titles, 12 studies were included in the final analysis with a total of 8864 participants. Five studies of high heterogeneity and risk of bias showed mixed results on the efficacy of e-IC on enrolment. Data of included studies suggested e-IC could improve comprehension and recall of study-related information. Meta-analysis could not be conducted due to different study designs and outcome measures and the predominantly qualitative findings.

Conclusion

Few published studies have investigated the impact of e-IC on enrolment and findings were mixed. e-IC may improve participant’s comprehension and recall of information. High-quality studies are needed to evaluate the potential benefit of e-IC to increase clinical trial enrolment.

Trial registration

PROSPEROCRD42021231035. Registration date: 19-Feb-2021.
MYC promotes fibroblast osteogenesis by regulating ALP and BMP2 to participate in ectopic ossification of ankylosing spondylitis
Authors: Jin Qianmei , Liu Yaoyang , Zhang Zhiguo , Wen Xingzhu , Chen Ziqiang , Tian Haijun , Kang Zijian , Wu Xin , Xu Huji
Published: February 2023

Background

Ectopic ossification is an important cause of disability in patients with ankylosing spondylitis (AS). Whether fibroblasts can transdifferentiate into osteoblasts and contribute to ossification remains unknown. This study aims to investigate the role of stem cell transcription factors (POU5F1, SOX2, KLF4, MYC, etc.) of fibroblasts in ectopic ossification in patients with AS.

Methods

Primary fibroblasts were isolated from the ligaments of patients with AS or osteoarthritis (OA). In an in vitro study, primary fibroblasts were cultured in osteogenic differentiation medium (ODM) to induce ossification. The level of mineralization was assessed by mineralization assay. The mRNA and protein levels of stem cell transcription factors were measured by real-time quantitative PCR (q-PCR) and western blotting. MYC was knocked down by infecting primary fibroblasts with lentivirus. The interactions between stem cell transcription factors and osteogenic genes were analysed by chromatin immunoprecipitation (ChIP). Recombinant human cytokines were added to the osteogenic model in vitro to evaluate their role in ossification.

Results

We found that MYC was elevated significantly in the process of inducing primary fibroblasts to differentiate into osteoblasts. In addition, the level of MYC was remarkably higher in AS ligaments than in OA ligaments. When MYC was knocked down, the expression of the osteogenic genes alkaline phosphatase (ALP) and bone morphogenic protein 2 (BMP2) was decreased, and the level of mineralization was reduced significantly. In addition, the ALP and BMP2 were confirmed to be the direct target genes of MYC. Furthermore, interferon-γ (IFN-γ), which showed high expression in AS ligaments, was found to promote the expression of MYC in fibroblasts in the process of ossification in vitro.

Conclusions

This study demonstrates the role of MYC in ectopic ossification. MYC may act as the critical bridge that links inflammation with ossification in AS, thus providing new insights into the molecular mechanisms of ectopic ossification in AS.
Maturity-onset diabetes of the young secondary to HNF1B variants (HNF1B-MODY): a series of 10 patients from a single diabetes center
Authors: Amaral Sara , Palha Ana , Bogalho Paula , Silva-Nunes José
Published: February 2023

Background

Maturity-Onset Diabetes of the Young (MODY) is an autosomal dominant condition and represents 1–5% of all cases of diabetes mellitus. MODY is often misdiagnosed as type 1 or type 2 diabetes. The rare subtype 5 (HNF1B-MODY) is due to hepatocyte nuclear factor 1β (HNF1B) molecular alteration and is remarkable for its multisystemic phenotypes characterized by a broad spectrum of pancreatic and extra-pancreatic clinical manifestations.

Methods

Retrospective study of patients with HNF1B-MODY diagnosis followed in the Centro Hospitalar Universitário Lisboa Central (Lisbon, Portugal). Demographic data, medical history, clinical and laboratory data, follow-up and treatment procedures were obtained from electronic medical records.

Results

We found 10 patients with HNF1B variants (7 index cases). The median age at diabetes diagnosis was 28 (IQR 24) years and the median age at HNF1B-MODY diagnosis was 40.5 (IQR 23) years. Six patients were initially misclassified as type 1 and 4 as type 2 diabetes. The average time between diabetes diagnosis and the diagnosis of HNF1B-MODY was 16.5 years. Diabetes was the first manifestation in half of the cases. The other half presented with kidney malformations and chronic kidney disease at pediatric age as the first manifestation. All these patients were submitted to kidney transplantation. Long-term diabetes complications included retinopathy (4/10), peripheral neuropathy (2/10) and ischemic cardiomyopathy (1/10). Other extra-pancreatic manifestations included liver test alterations (4/10) and congenital malformation of the female reproductive tract (1/6). History of a first-degree relative with diabetes and/or nephropathy diagnosed at a young age was present in 5 of the 7 index cases.

Conclusions

Despite being a rare disease, HNF1B-MODY is underdiagnosed and often misclassified. It should be suspected in patients with diabetes and CKD, especially when diabetes appears at a young age, a family history is present, and nephropathy appears before/shortly after the diagnosis of diabetes. Presence of unexplained liver disease increases the degree of suspicion for HNF1B-MODY. Early diagnosis is important to minimize complications and to allow familial screening and pre-conception genetic counseling.

Trial registration not applicable due to the retrospective nature of the study, non-interventional.
Nonrestorative sleep is a risk factor for metabolic syndrome in the general Japanese population
Authors: Otsuka Yuichiro , Kaneita Yoshitaka , Tanaka Katsutoshi , Itani Osamu , Kaneko Yoshiyuki , Suzuki Masahiro , Matsumoto Yuuki , Kuriyama Kenichi
Published: February 2023

Background

This longitudinal study aimed to investigate the effects of nonrestorative sleep on developing metabolic syndrome (MetS) and related diseases in a general Japanese middle-aged population.

Methods

Overall, 83,224 adults without MetS (mean age: 51.5 ± 3.5 years) from the Health Insurance Association in Japan were followed up for a maximum of 8 years between 2011 and 2019. The Cox proportional hazard method was used to determine whether nonrestorative sleep, assessed using a single-item question, was significantly associated with the respective development of MetS, obesity, hypertension, diabetes, and dyslipidemia. The MetS criteria were adopted by the Examination Committee for Criteria of Metabolic Syndrome in Japan.

Results

The mean follow-up duration was 6.0 years. The incidence rate of MetS was 50.1 person-years/1,000 during the study period. Data suggested that nonrestorative sleep was associated with MetS (hazard ratio [HR]: 1.12, 95% confidence interval [CI]: 1.08–1.16) and other disorders, such as obesity (HR: 1.07, 95% CI: 1.02–1.12), hypertension (HR: 1.07, 95% CI: 1.04–1.11), and diabetes (HR: 1.07, 95% CI: 1.01–1.12) but not with dyslipidemia (HR: 1.00, 95% CI: 0.97–1.03).

Conclusions

Nonrestorative sleep is associated with the development of MetS and many of its core components in the middle-aged Japanese population. Therefore, assessing nonrestorative sleep may help identify individuals at a risk of MetS development.
How disability severity is associated with changes in physical activity and inactivity from adolescence to young adulthood
Authors: Jung Jihoon , Park Seungyeon , Lee Chung Gun
Published: February 2023

Background

Disabilities may play a different role in determining people’s physical activity (PA) and physical inactivity (PI) levels when they go through multiple lifetime transitions (e.g., graduation, marriage) between adolescence and young adulthood. This study investigates how disability severity is associated with changes in PA and PI engagement levels, focusing on adolescence and young adulthood, when the patterns of PA and PI are usually formed.

Methods

The study employed data from Waves 1 (adolescence) and 4 (young adulthood) of the National Longitudinal Study of Adolescent Health, which covers a total of 15,701 subjects. We first categorized subjects into 4 disability groups: no, minimal, mild, or moderate/severe disability and/or limitation. We then calculated the differences in PA and PI engagement levels between Waves 1 and 4 at the individual level to measure how much the PA and PI levels of individuals changed between adolescence and young adulthood. Finally, we used two separate multinomial logistic regression models for PA and PI to investigate the relationships between disability severity and the changes in PA and PI engagement levels between the two periods after controlling for multiple demographic (age, race, sex) and socioeconomic (household income level, education level) variables.

Results

We showed that individuals with minimal disabilities were more likely to decrease their PA levels during transitions from adolescence to young adulthood than those without disabilities.

Our findings also revealed that individuals with moderate to severe disabilities tended to have higher PI levels than individuals without disabilities when they were young adults. Furthermore, we found that people above the poverty level were more likely to increase their PA levels to a certain degree compared to people in the group below or near the poverty level.

Conclusions

Our study partially indicates that individuals with disabilities are more vulnerable to unhealthy lifestyles due to a lack of PA engagement and increased PI time compared to people without disabilities. We recommend that health agencies at the state and federal levels allocate more resources for individuals with disabilities to mitigate health disparities between those with and without disabilities.
Emerging roles of m6A RNA modification in cancer therapeutic resistance
Authors: Liu Wei-Wei , Zhang Zhong-Yuan , Wang Fei , Wang Hao
Published: February 2023

Marvelous advancements have been made in cancer therapies to improve clinical outcomes over the years. However, therapeutic resistance has always been a major difficulty in cancer therapy, with extremely complicated mechanisms remain elusive. N6-methyladenosine (m6A) RNA modification, a hotspot in epigenetics, has gained growing attention as a potential determinant of therapeutic resistance. As the most prevalent RNA modification, m6A is involved in every links of RNA metabolism, including RNA splicing, nuclear export, translation and stability. Three kinds of regulators, “writer” (methyltransferase), “eraser” (demethylase) and “reader” (m6A binding proteins), together orchestrate the dynamic and reversible process of m6A modification. Herein, we primarily reviewed the regulatory mechanisms of m6A in therapeutic resistance, including chemotherapy, targeted therapy, radiotherapy and immunotherapy. Then we discussed the clinical potential of m6A modification to overcome resistance and optimize cancer therapy. Additionally, we proposed existing problems in current research and prospects for future research.
Complement-related molecular classification and a gene signature for lung adenocarcinoma
Authors: Zhang Lin , Yang Yannan , Lin Weihao , Shao Fei , Gao Yibo , He Jie
Published: February 2023

Background

Lung adenocarcinoma (LUAD) is a major cause of cancer-related death worldwide, and the roles of complement-related genes in it have not been thoroughly investigated yet. In the study, we aimed to systemically examine the prognostic performance of complement-related genes, classify the patients into two different clusters and stratify the patients into different risk groups using a complement-related gene signature.

Methods

To achieve this, clustering analyses, Kaplan–Meier survival analyses, immune infiltration analyses were performed. LUAD patients from The Cancer Genome Atlas (TCGA) were classified into two subtypes (C1 and C2). A prognostic signature, consisting of four complement-related genes, was established using TCGA-LUAD cohort and validated in six Gene Expression Omnibus datasets and an independent cohort from our center.

Results

The prognosis of C2 patients is better than that of C1 patients and the prognosis of low risk patients is significantly better than high risk patients across the public datasets. In our cohort, the OS of patients in low risk group is better than that in high risk group but the difference is not significant. Patients with a lower risk score were characterized by a higher immune score, a higher level of BTLA, higher infiltration levels of T cells, B lineage, myeloid dendritic cells, neutrophils, endothelial cells, and a lower infiltration level of fibroblast.

Conclusions

In summary, our study has established a new classification method and developed a prognostic signature for LUAD, while future studies are needed for further exploration of the underlying mechanism.
Strong conductivity enhancement of La-doped BaSnO3 transparent films on Al2O3 with the assistance of templated epitaxy for electromagnetic shielding in extreme environments
Authors: Ha Youngkyoung , Lee Shinbuhm
Published: February 2023

Transparent La-doped BaSnO3 (BLSO) epitaxial films grown on expensive perovskites show promising conductive properties. However, BLSO films on Al2O3 have a higher sheet resistance by two orders of magnitude. In this research, the sheet resistance of BLSO films is recovered to that of the single-crystalline level by growing (111)-oriented BLSO epitaxial films on (0001)Al2O3 with the assistance of (111)BaZrO3/MgO template bilayer. Their intriguing transparent conductive properties, including high electromagnetic shielding effectiveness (~ 13.2 dB at 10 GHz) and high stability at 700 °C, will promote stable optoelectronic applications in extreme environments with economic benefits.

Graphical Abstract
On the drag reduction mechanism of hypersonic turbulent boundary layers subject to heated wall blowing
Authors: Liu Qiang , Luo Zhenbing , Zhou Yan , Xie Wei , Dong Siwei
Published: February 2023

Turbulence drag reduction is of great significance for the range increase of hypersonic flight vehicles. The proposed velocity-temperature coupling control method (Liu et al, Phys Rev Fluids 6:044603, 2021) is further extended to the hypersonic turbulent boundary layer. Direct numerical simulation results of four comparative cases show that the heated wall blowing achieves a drag reduction rate of 10.58%, which is about the sum of wall blowing (5.27%) and wall heating (6.35%). By evaluating the control efficiency, however, it is found that heated wall blowing is not as good as wall blowing and cannot obtain net energy saving rate. The modified FIK decompositions of skin friction coefficient indicate that the cliffy decrease of the mean convection term is the primary contribution for the drag reduction. Effects of the proposed control measure on turbulence statistics and coherent structures are also analyzed. Streamwise vortex is found to be away from the wall, thus leading to a lower friction drag.
Enhancing review criteria for dissemination and implementation science grants
Authors: Stadnick Nicole A. , Viglione Clare , Crable Erika L. , Montoya Jessica L. , Gholami Maryam , Su Irene , Rabin Borsika
Published: February 2023

Background

The existing grant review criteria do not consider unique methods and priorities of Dissemination and Implementation Science (DIS). The ImplemeNtation and Improvement Science Proposals Evaluation CriTeria (INSPECT) scoring system includes 10 criteria based on Proctor et al.’s “ten key ingredients” and was developed to support the assessment of DIS research proposals. We describe how we adapted INSPECT and used it in combination with the NIH scoring system to evaluate pilot DIS study proposals through our DIS Center.

Methods

We adapted INSPECT to broaden considerations for diverse DIS settings and concepts (e.g., explicitly including dissemination and implementation methods). Five PhD-level researchers with intermediate to advanced DIS knowledge were trained to conduct reviews of seven grant applications using both the INSPECT and NIH criteria. The INSPECT overall scores range from 0 to 30 (higher scores are better), and the NIH overall scores range from 1 to 9 (lower scores are better). Each grant was independently reviewed by two reviewers, then discussed in a group meeting to compare the experiences using both criteria to evaluate the proposal and to finalize scoring decisions. A follow-up survey was sent to grant reviewers to solicit further reflections on each scoring criterion.

Results

Averaged across reviewers, the INSPECT overall scores ranged from 13 to 24, while the NIH overall scores ranged from 2 to 5. Reviewer reflections highlighted the unique value and utility for each scoring criterion. The NIH criteria had a broad scientific purview and were better suited to evaluate more effectiveness-focused and pre-implementation proposals not testing implementation strategies. The INSPECT criteria were easier to rate in terms of the quality of integrating DIS considerations into the proposal and to assess the potential for generalizability, real-world feasibility, and impact. Overall, reviewers noted that INSPECT was a helpful tool to guide DIS research proposal writing.

Conclusions

We confirmed complementarity in using both scoring criteria in our pilot study grant proposal review and highlighted the utility of INSPECT as a potential DIS resource for training and capacity building. Possible refinements to INSPECT include more explicit reviewer guidance on assessing pre-implementation proposals, providing reviewers with the opportunity to submit written commentary with each numerical rating, and greater clarity on rating criteria with overlapping descriptions.
Optimization of sewage sampling for wastewater-based epidemiology through stochastic modeling
Authors: Martin Max , Goethals Paul , Newhart Kathryn , Rhodes Emily , Vogel Jason , Stevenson Bradley
Published: February 2023

The proliferation of the SARS-CoV-2 global pandemic has brought to attention the need for epidemiological tools that can detect diseases in specific geographical areas through non-contact means. Such methods may protect those potentially infected by facilitating early quarantine policies to prevent the spread of the disease. Sampling of municipal wastewater has been studied as a plausible solution to detect pathogen spread, even from asymptomatic patients. However, many challenges exist in wastewater-based epidemiology such as identifying a representative sample for a population, determining the appropriate sample size, and establishing the right time and place for samples. In this work, a new approach to address these questions is assessed using stochastic modeling to represent wastewater sampling given a particular community of interest. Using estimates for various process parameters, inferences on the population infected are generated with Monte Carlo simulation output. A case study at the University of Oklahoma is examined to calibrate and evaluate the model output. Finally, extensions are provided for more efficient wastewater sampling campaigns in the future. This research provides greater insight into the effects of viral load, the percentage of the population infected, and sampling time on mean SARS-CoV-2 concentration through simulation. In doing so, an earlier warning of infection for a given population may be obtained and aid in reducing the spread of viruses.