bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractIn 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

Abstract
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

AbstractBackgroundEnrolment 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.MethodsEmbase, 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.ResultsFrom 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.ConclusionFew 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 registrationPROSPEROCRD42021231035. 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

Abstract

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

Abstract
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

Abstract
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

Abstract
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

AbstractMarvelous 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

Abstract
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

AbstractTransparent 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

AbstractTurbulence 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

Abstract
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.