bluuebunny/crossref_metadata_2025_split huggingface dataset:
Five long non-coding RNAs establish a prognostic nomogram and construct a competing endogenous RNA network in the progression of non-small cell lung cancer
Authors: Yu Yong , Ren Kaiming 
Published: April 2021

Abstract
Background
Accumulating evidence has revealed that long non-coding RNAs (lncRNAs) play vital roles in the progression of non-small cell lung cancer (NSCLC). But the relationship between lncRNAs and survival outcome of NSCLC remains to be explored. Therefore, we attempt to figure out their survival roles and molecular connection in NSCLC.

Methods
By analyzing the transcriptome profiling of NSCLC from TCGA databases, we divided patients into three groups, and identified differentially expressed lncRNAs (DELs) of each group. Next, we explored the prognostic roles of common DELs by univariate and multivariate Cox analysis, Lasson, and Kaplan-Meier analysis. Additionally, we assessed and compared the prognostic accuracy of 5 lncRNAs through ROC curves and AUC values. Ultimately, we detected their potential function by enrichment analysis and molecular connection through establishing a competing endogenous RNA (ceRNA) network.

Results
One hundred ninety-seven common DELs were spotted. And we successfully screened out 5 lncRNAs related to the patient’s survival, including LINC01833, AC112206.2, FAM83A-AS1, BANCR, and HOTAIR. Combing with age and AJCC stage, we constructed a nomogram that prognostic prediction was superior to the traditional parameters. Furthermore, 275 qualified mRNAs related to 5 lncRNAs were spotted. Functional analysis indicates that these lncRNAs act key roles in the progression of NSCLC, such as P53 and cell cycle signaling pathway. And ceRNA network also suggests that these lncRNAs are tightly connected with tumor progression.

Conclusions
A nomogram and ceRNA network based on 5 lncRNAs indicate that there can effectively predict the overall survival of NSCLC and potentially serve as a therapeutic guide for NSCLC.
Irrational use of antibiotics in Iran from the perspective of complex adaptive systems: redefining the challenge
Authors: Sharif Zahra , Peiravian Farzad , Salamzadeh Jamshid , Mohammadi Nastaran Keshavarz , Jalalimanesh Ammar 
Published: April 2021

AbstractBackgroundIrrational use of antibiotics is proving to be a major concern to the health systems globally. This results in antibiotics resistance and increases health care costs. In Iran, despite many years of research, appreciable efforts, and policymaking to avoid irrational use of antibiotics, yet indicators show suboptimal use of antibiotics, pointing to an urgent need for adopting alternative approaches to further understand the problem and to offer new solutions. Applying the Complex Adaptive Systems (CAS) theory, to explore and research health systems and their challenges has become popular. Therefore, this study aimed to better understand the complexity of the irrational use of antibiotics in Iran and to propose potential solutions.MethodThis research utilized a CAS observatory tool to qualitatively collect and analyse data. Twenty interviews and two Focus Group discussions were conducted. The data was enriched with policy document reviews to fully understand the system. MAXQDA software was used to organize and analyze the data.ResultWe could identify several diverse and heterogeneous, yet highly interdependent agents operating at different levels in the antibiotics use system in Iran. The network structure and its adaptive emergent behavior, information flow, governing rules, feedback and values of the system, and the way they interact were identified. The findings described antibiotics use as emergent behavior that is formed by an interplay of many factors and agents over time. According to this study, insufficient and ineffective interaction and information flow regarding antibiotics between agents are among key causes of irrational antibiotics use in Iran. Results showed that effective rules to minimize irrational use of antibiotics are missing or can be easily disobeyed. The gaps and weaknesses of the system which need redesigning or modification were recognized as well.ConclusionThe study suggests re-engineering the system by implementing several system-level changes including establishing strong, timely, and effective interactions between identified stakeholders, which facilitate information flow and provision of on-time feedback, and create win-win rules in a participatory manner with stakeholders and the distributed control system.
No changes in adolescent’s sedentary behaviour across Europe between 2002 and 2017
Authors: López-Fernández J. , López-Valenciano A. , Mayo X. , Liguori G. , Lamb M. A. , Copeland R. J. , Jiménez A. 
Published: April 2021

Abstract
Background
Public health organizations have been alerted to the high levels of sedentary behaviour (SB) among adolescents as well as to the health and social consequences of excess sedentary time. However, SB changes of the European Union (EU) adolescents over time have not been reported yet. This study aimed to identify SB of the EU adolescents (15–17 years) in four-time points (2002, 2005, 2013 and 2017) and to analyse the prevalence of SB according to the sex.

Methods
SB of 2542 adolescents (1335 boys and 1207 girls) as a whole sample and country-by-country was analysed in 2002, 2005, 2013, and 2017 using the Sport and Physical Activity EU Special Eurobarometers’ data. SB was measured using the sitting time question from the short version of the International Physical Activity Questionnaire (IPAQ), such that 4h30min of daily sitting time was the delineating point to determine excess SB behaviour (≥4h30min of sitting time) or not (≤4h30min of sitting time). A χ2 test was used to compare the prevalence of SB between survey years. Furthermore, SB prevalence between sexes was analysed using a Z-Score test for two population proportions.

Results
The prevalence of SB among EU adolescents across each of the four survey years ranged from 74.2 and 76.8%, rates that are considered high. High levels of SB were also displayed by both sexes (girls: 76.8 to 81.2%; boys: 71.7 to 76.7%). No significant differences in the prevalence of SB among years (p > 0.05) were found for the whole sample, and for either girls or boys. Also, no significant differences in the prevalence of SB between girls and boys were found.

Conclusion
The SB prevalence in European adolescents is extremely high (76.8% in 2017) with no differences between girls and boys. No significant improvements have been seen between 2002 and 2017. Eurobarometer should increase the adolescents’ sample to make possible benchmarking comparisons among the EU countries and extend the survey to the younger children population.
Development and internal validation of a prediction model of prostate cancer on initial transperineal template-guided prostate biopsy
Authors: Chen Yuliang , Zhou Zhien , Zhou Yi , Wu Xingcheng , Xiao Yu , Ji Zhigang , Li Hanzhong , Yan Weigang 
Published: April 2021

AbstractBackgroundDue to the invasiveness of prostate biopsy, a prediction model of the individual risk of a positive biopsy result could be helpful to guide clinical decision-making. Most existing models are based on transrectal ultrasonography (TRUS)-guided biopsy. On the other hand, transperineal template-guided prostate biopsy (TTPB) has been reported to be more accurate in evaluating prostate cancer. The objective of this study is to develop a prediction model of the detection of high-grade prostate cancer (HGPC) on initial TTPB.ResultA total of 1352 out of 3794 (35.6%) patients were diagnosed with prostate cancer, 848 of whom had tumour with Grade Group 2–5. Age, PSA, PV, DRE and f/t PSA are independent predictors of HGPC with p < 0.001. The model showed good discrimination ability (c-index 0.886) and calibration during internal validation and good clinical performance was observed through decision curve analysis. The external validation of CPCC-RC, an existing model, demonstrated that models based on TRUS-guided biopsy may underestimate the risk of HGPC in patients who underwent TTPB.ConclusionWe established a prediction model which showed good discrimination ability and calibration in predicting the detection of HGPC by initial TTPB. This model can be used to aid clinical decision making for Chinese patients and other Asian populations with similar genomic backgrounds, after external validations are conducted to further confirm its clinical applicability.
Estimation of salivary matrix metalloproteinases- 12 (MMP- 12) levels among patients presenting with oral submucous fibrosis and oral squamous cell carcinoma
Authors: Saleem Zohra , Shaikh Abdul Hafeez , Zaman Uzma , Ahmed Shaheen , Majeed Muhammad Mansoor , Kazmi Anum , Farooqui Waqas Ahmed 
Published: April 2021

AbstractBackgroundOral squamous cell carcinoma is a global threat and accounts for approximately 90% of malignant oral lesions. The emergence of oral carcinoma is linked to precancerous lesions, which act as precursors of the disease. Matrix metalloproteinases appear to play a significant role in the pathogenesis of both precancerous conditions and oral malignancies due to their participation in remodeling of the extracellular matrix.MethodologyThis is an analytical study conducted at Dow University of Health Sciences, Pakistan. Unstimulated saliva samples were collected from healthy, oral submucous fibrosis and oral squamous cell carcinoma patients. The level of MMP-12 was estimated using enzyme-linked immunosorbent assay. One-way Analysis of variance was run to determine if MMP-12 levels differ between the three groups, which was preceded by post hoc Tuckey test. MMP-12 cut off values were determined using Receiver operating characteristic curve.ResultsA significant difference in salivary MMP-12 expression was observed in OSF and OSCC (p < 0.001). The expression of salivary MMP-12 was higher in OSF and OSCC patients as compared to the healthy group (p < 0.001). The mean MMP-12 expression in OSCC appeared higher than in OSF cases (p < 0.05). MMP-12 value of$$\ge$$≥4.05 ng/ml and$$\ge$$≥4.20 ng/ml is predictive of OSF and OSCC respectively, with 100% sensitivity and specificity (p < 0.001).ConclusionIncreased expression of MMP-12 appears as the healthy patient advances to OSF and OSCC. The study results also demonstrate higher MMP-12 expression in OSCC patients as compared to OSF. Therefore, the estimation of salivary MMP-12 serves as a valuable non-invasive early diagnostic tool in diagnosing oral submucous fibrosis and oral squamous cell carcinoma.
Automatic glaucoma detection based on transfer induced attention network
Authors: Xu Xi , Guan Yu , Li Jianqiang , Ma Zerui , Zhang Li , Li Li 
Published: April 2021

Abstract
Background
Glaucoma is one of the causes that leads to irreversible vision loss. Automatic glaucoma detection based on fundus images has been widely studied in recent years. However, existing methods mainly depend on a considerable amount of labeled data to train the model, which is a serious constraint for real-world glaucoma detection.

Methods
In this paper, we introduce a transfer learning technique that leverages the fundus feature learned from similar ophthalmic data to facilitate diagnosing glaucoma. Specifically, a Transfer Induced Attention Network (TIA-Net) for automatic glaucoma detection is proposed, which extracts the discriminative features that fully characterize the glaucoma-related deep patterns under limited supervision. By integrating the channel-wise attention and maximum mean discrepancy, our proposed method can achieve a smooth transition between general and specific features, thus enhancing the feature transferability.

Results
To delimit the boundary between general and specific features precisely, we first investigate how many layers should be transferred during training with the source dataset network. Next, we compare our proposed model to previously mentioned methods and analyze their performance. Finally, with the advantages of the model design, we provide a transparent and interpretable transferring visualization by highlighting the key specific features in each fundus image. We evaluate the effectiveness of TIA-Net on two real clinical datasets and achieve an accuracy of 85.7%/76.6%, sensitivity of 84.9%/75.3%, specificity of 86.9%/77.2%, and AUC of 0.929 and 0.835, far better than other state-of-the-art methods.

Conclusion
Different from previous studies applied classic CNN models to transfer features from the non-medical dataset, we leverage knowledge from the similar ophthalmic dataset and propose an attention-based deep transfer learning model for the glaucoma diagnosis task. Extensive experiments on two real clinical datasets show that our TIA-Net outperforms other state-of-the-art methods, and meanwhile, it has certain medical value and significance for the early diagnosis of other medical tasks.
A comparative performance analysis of the International Classification of Functioning, Disability and Health and the Item-Perspective Classification framework for classifying the content of patient reported outcome measures
Authors: Rosa Derek , MacDermid Joy , Klubowicz Dorota 
Published: April 2021

Abstract
Background
Standardized coding of the content presented in patient reported outcome measures can be achieved using classification frameworks, and the resulting data can be used for ascertaining content validity or comparative analyses. The International Classification of Functioning (ICF) is a framework with a detailed conceptual structure that has been successfully utilized for such purposes through established coding procedures. The Item Perspective Classification (IPC) framework is a newly developed relational coding system that classifies the respondent perspective and conceptual domains addressed in items. The purpose of this study was to compare and describe the performance of these two frameworks when used alone, and in conjunction, for the generation of data pertaining to the content of patient reported outcome measures.

Methods
Six health-related quality of life questionnaires with a total of 159 items were classified by two raters using the Item Perspective Classification framework in conjunction with the International Classification of Functioning. Framework performance indicators included: classification capacity (percent of items amenable to successful classification), coding efficiency (number of codes required to classify items), and content overlap detection (percent of items sharing identical classification codes with at least one other item). Inter-rater reliability of item coding was determined using Krippendorff's alpha.

Results
Classification capacity of the IPC framework was 97%, coding efficiency 26, and content overlap detection was 95%; whereas respective values for the ICF were 68%, 114, and 58%. When used in conjunction values were 63%, 129, and 30%. Krippendorff's alpha exceeded 0.97 for all 3 classification indices.

Conclusion
Inter-rater agreement on classification data was excellent. The IPC framework provided a unique classification of the respondent’s judgment during item response and classified more items using fewer categories, indicated greater content overlap across items and was able to describe the relationship between multiple concepts presented within the context of a single item. The ICF provided a unique classification of item content relating to aspects of disability and generated more detailed and precise descriptions. A combined approach provided a rich description (detailed codes) with each framework providing complementary information. The benefits of this approach in instrument development and content validation require further investigation.
Clinicopathologic features of metastatic small cell carcinoma of the prostate to the liver: a series of four cases
Authors: Bell Phoenix D. , Huber Aaron R. , Agostini-Vulaj Diana 
Published: April 2021

Abstract
Background
Small cell neuroendocrine carcinoma of the prostate (SCNECP) is a rare, aggressive subtype of prostate carcinoma. Most SCNECP arise from conventional prostate adenocarcinoma (CPAC) treated with androgen deprivation therapy (ADT).

Case presentations
We identified four cases of CPAC treated with ADT, which evolved to SCNECP with liver metastasis. The average interval between the diagnosis of CPAC and SCNECP was 102 months (range: 12 to 168). Histologically, the tumors showed nests of cells with high nuclear:cytoplasmic ratios, granular chromatin, and frequent mitoses. All cases were synaptophysin, chromogranin, and AE1/AE3 positive, with a Ki-67 labeling index ≥70%. NKX3.1 was negative in all but one case and TTF-1 was positive in half. Weak ERG positivity by IHC was seen in one case which also demonstrated the TMPRSS2-ERG gene rearrangement; all other cases were negative for ERG by IHC. Serum prostate specific antigen (PSA) levels were normal to near-normal in all. The median interval between the diagnosis of SCNECP and death was 3.25 months (range: 0.75 to 26).

Conclusions
Our case series highlights the importance of considering a prostate primary, even in the setting of normal PSA levels and loss of prostate markers, when diagnosing neuroendocrine carcinoma in the liver. Further, we emphasize the significance of diagnosing SCNECP that metastasizes to the liver, as it portends a particularly dismal prognosis.
Perceptions of the barriers, facilitators, outcomes, and helpfulness of strategies to implement screening, brief intervention, and referral to treatment in acute care
Authors: Keen Alyson , Thoele Kelli , Oruche Ukamaka , Newhouse Robin 
Published: April 2021

Abstract
Background
Screening, Brief Intervention, and Referral to Treatment (SBIRT) is a clinical intervention used to address alcohol and illicit drug use. SBIRT use has resulted in positive health and social outcomes; however, SBIRT implementation remains low. Research on implementing interventions, such as SBIRT, lacks information about challenges and successes related to implementation. The Expert Recommendations for Implementing Change (ERIC) provides a framework to guide comprehension, clarity, and relevance of strategies available for implementation research. This framework was applied to qualitative feedback gathered from site coordinators (SCs) leading SBIRT implementation. The purpose of this study was to describe the SCs’ experiences pertaining to SBIRT implementation across a health system.

Methods
Within the context of a larger parent study, a semi-structured interview guide was used to capture 14 SCs’ perceptions of the barriers, facilitators, and outcomes pertaining to SBIRT implementation. Qualitative data were analyzed using standard content analytic procedures. A follow-up survey was developed based on 14 strategies identified from qualitative data and was administered electronically to determine the SC’s perceptions of the most helpful implementation strategies on a scale of 1 (least helpful) to 5 (most helpful).

Results
All 14 invited SCs participated in the SBIRT implementation interview, and 11 of 14 (79%) responded to the follow-up survey. Within the categories of barriers, facilitators, and outcomes, 25 subthemes emerged. The most helpful implementation strategies were reexamining the implementation (M = 4.38; n = 8), providing ongoing consultation (M = 4.13; n = 8), auditing and providing feedback (M = 4.1; n = 10), developing education materials (M = 4.1; n = 10), identifying and preparing champions (M = 4; n = 7), and tailoring strategies (M = 4; n = 7).

Conclusion
SCs who led implementation efforts within a large healthcare system identified several barriers and facilitators to the implementation of SBIRT. Additionally, they identified clinician-related outcomes associated with SBIRT implementation into practice as well as strategies that were helpful in the implementation process. This information can inform the implementation of SBIRT and other interventions in acute care settings.
G-quadruplexes are transcription factor binding hubs in human chromatin
Authors: Spiegel Jochen , Cuesta Sergio Martínez , Adhikari Santosh , Hänsel-Hertsch Robert , Tannahill David , Balasubramanian Shankar 
Published: April 2021

AbstractBackgroundThe binding of transcription factors (TF) to genomic targets is critical in the regulation of gene expression. Short, double-stranded DNA sequence motifs are routinely implicated in TF recruitment, but many questions remain on how binding site specificity is governed.ResultsHerein, we reveal a previously unappreciated role for DNA secondary structures as key features for TF recruitment. In a systematic, genome-wide study, we discover that endogenous G-quadruplex secondary structures (G4s) are prevalent TF binding sites in human chromatin. Certain TFs bind G4s with affinities comparable to double-stranded DNA targets. We demonstrate that, in a chromatin context, this binding interaction is competed out with a small molecule. Notably, endogenous G4s are prominent binding sites for a large number of TFs, particularly at promoters of highly expressed genes.ConclusionsOur results reveal a novel non-canonical mechanism for TF binding whereby G4s operate as common binding hubs for many different TFs to promote increased transcription.
Clinical course, radiological findings and late outcome in preterm infant with suspected vertical transmission born to a mother with severe COVID-19 pneumonia: a case report
Authors: Farhadi Roya , Mehrpisheh Shahrokh , Ghaffari Vajiheh , Haghshenas Mohammadreza , Ebadi Aghdas 
Published: April 2021

Abstract
Background
Vertical transmission of coronavirus disease 2019 (COVID-19) from mother to newborn infant is doubtful, and very little is known about disease severity and neonatal outcome.

Case presentation
We present a preterm Iranian infant born to a Persian mother with severe COVID-19 pneumonia. The mother underwent cesarean delivery, and amniotic fluid yielded a positive result for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by real-time reverse transcription polymerase chain reaction (RT-PCR). The newborn infant showed early-onset infection with SARS-CoV-2 confirmed on pharyngeal swabs by RT-PCR assay within 24 hours after birth, suggesting vertical transmission. Unfortunately, the mother died 14 days after delivery. We describe the clinical course and outcome of the infant up to 7 months of age.

Conclusion
COVID-19 infection in pregnant women may increase maternal morbidity, mortality and possibly vertical transmission in severe cases. However, it does not seem to progress to serious early or late neonatal complications.