bluuebunny/crossref_metadata_2025_split huggingface dataset:
The use of ultrasound in the emergency department for the detection of thoracic outlet syndrome: A single case study
Authors: Tung-Chen Yale , Marín-Baselga Raquel , Tejada-Sorados Renzo , Enfedaque-Castilla Israel 
Published: July 2020

Introduction Thoracic outlet syndrome (TOS) refers to a spectrum of syndromes related to the compression of the brachial plexus (neurogenic TOS), subclavian vein or artery in the general region of the thoracic outlet, which is the area just above the first rib and behind the clavicle. Case report We report a 27-year-old healthy man who presented to the emergency department with right upper limb pain, tingling and weakness. Point-of-care ultrasonography was performed following a dynamic protocol in the supraclavicular fossa in the right upper limb. A congenital cervical rib, as well as narrowing of the costoclavicular gap, causing vein, artery and spinal roots compression was evidenced. This maneuver reproduced the symptoms, confirming the suspicion of neurogenic TOS. Discussion Early diagnosis is important, because the neurogenic compression associated with neurogenic TOS, if prolonged, can lead to muscle weakness and atrophy, being irreversible. Selected patients with neurogenic TOS who have progressive weakness, disabling pain, or who have failed to improve with conservative measures are considered for first rib resection. Conclusion Using the dynamic approach during point-of-care ultrasonography examination, in combination with physical examination and cervical radiography, could help identify neurogenic TOS.
Early COPD: current evidence for diagnosis and management
Authors: Fazleen Aishath , Wilkinson Tom 
Published: July 2020

Chronic obstructive pulmonary disease (COPD) affects one-tenth of the world’s population and has been identified as a major global unmet health need by the World Health Organisation, which predicts that within 10 years, COPD will become the third leading cause of death. Despite active research, there have been no recent major strides in terms of disease modifying treatment for COPD; smoking cessation remains the only intervention known to alter disease progression and improve mortality. As established COPD is a key driver of disease burden, earlier diagnosis coupled with disease-modifying intervention carries promise as a route to address this global health priority. The concept of early COPD is emerging as an area of focus for research and consideration of new treatment modalities, as it has been hypothesised that intervention at this stage may potentially halt or reverse the disease process. However, at present, a globally accepted criteria for defining early COPD does not exist. Several studies propose small airways disease as the earliest stage in the development of COPD, and this has been demonstrated to be a precursor to development of emphysema and to correlate with subsequent development of airflow obstruction. However, treatment strategies for early disease, which pre-date the development of airflow obstruction, remain uncertain. This review addresses the rationale and current evidence base for the diagnosis and treatment of early COPD and highlights the challenges of implementing trials and clinical pathways to address COPD earlier in the life course, particularly in the absence of a universally accepted definition of COPD. The reviews of this paper are available via the supplemental material section.
Adverse outcome of acute splenic sequestration crisis in pregnancy
Authors: Malinowski Ann Kinga , Parrish Jacqueline , D’Souza Rohan , Kuo Kevin HM , Ward Richard , Shehata Nadine 
Published: July 2020

Background Acute splenic sequestration crisis, characterized by abrupt fall in hemoglobin, splenomegaly, hypovolemia, and often thrombocytopenia, occurs infrequently in adults with sickle cell disease and extremely rarely during pregnancy. Case A 25-year-old woman with HbSC presented at 33 weeks’ gestation with vaso-occlusive pain. Sudden worsening of abdominal pain and non-reassuring fetal surveillance on day 3 of admission led to emergent delivery. Acute splenic sequestration crisis was the diagnosis of exclusion based on clinical presentation and intra-operative hemoglobin of 37 g/L. Five- and 10-minute Apgar scores were 4. Neonatal brain magnetic resonance imaging revealed significant diffuse white matter abnormalities. Conclusion Acute splenic sequestration crisis in pregnancy must be considered in the differential diagnosis for this patient population as it can evolve rapidly and lead to maternal and fetal compromise.
Do Stairs Inhibit Seniors Who Live on Upper Floors From Going Out?
Authors: Yu Yifan , Chen Zheng , Bu Jiatian , Zhang Qinglai 
Published: July 2020

Background: Walk-up buildings are common in China today since they were almost the only type of residential buildings constructed from the 1950s to the 1990s. Objectives: This study examined how a vertical mobility obstacle, that is, mandatory stair climbing in walk-up residential buildings, may impact whether seniors go outdoors. Methods: We collected and examined 1,608 valid data records from 64 Chinese senior participants in Shanghai wearing Fitbit HR wristbands that tracked their mobility and physical activity for 31 consecutive days. Multilevel mixed-effects logistic regressions were performed on the binary leaving-home-or-not probability by the level of vertical obstacles controlled for physical–demographic factors, socioeconomic factors, outdoor activity habits, and weather. Results: Our observations revealed that each floor above ground level reduced the likelihood of outdoor trips by approximately one third per floor. After controlling for the physical, demographic, and socioeconomic factors of the participants as well as weather and holidays, we found that significantly fewer going-out incidents were also associated with more frequent outdoor activities within the community, especially in paved areas, but no associations were observed with self-reported visit frequencies to green spaces, senior centers within the community, or other places outside the community. Conclusion: This study offered the in situ observation that seniors’ probability of leaving their homes is correlated with the degree of vertical circulation as a mobility barrier (i.e., the number of stairs between their living space and access to the outdoors), which may impact policy making for regulations concerning elevators in residential codes and renovations.
Differentiation of Clinical Patterns Associated With Rhinologic Disease
Authors: Parsel Sean M. , Riley Charles A. , Todd Cameron A. , Thomas Andrew J. , McCoul Edward D. 
Published: July 2020

Background Common rhinologic diagnoses have similar presentations with a varying degree of overlap. Patterns may exist within clinical data that can be useful for early diagnosis and predicting outcomes. Objective To explore the feasibility of artificial intelligence to differentiate patterns in patient data in order to develop clinically-meaningful diagnostic groups. Methods A cross-sectional study of prospectively-acquired patient data at a tertiary rhinology clinic was performed. Data extracted included objective findings on nasal endoscopy, patient reported quality of life (PRQOL) instrument ratings, peripheral eosinophil fraction, and past medical history. Unsupervised non-hierarchical cluster analysis was performed to discover patterns in the data using 22 input variables. Results A total of 545 patients were analyzed after application of inclusion and exclusion criteria yielding 7 unique patient clusters, highly dependent on PRQOL scores and demographics. The clusters were clinically-relevant with distinct characteristics. Chronic rhinosinusitis without nasal polyposis (CRSsNP) was associated with two clusters having low frequencies of asthma and low eosinophil fractions. Chronic rhinosinusitis with nasal polyposis (CRSwNP) was associated with high frequency of asthma, mean (standard deviation [SD]) NOSE scores of 66 (19) and SNOT-22 scores of 41 (15), and high eosinophil fractions. AR was present in multiple clusters. RARS was associated with the youngest population with mean (SD) NOSE score of 54 (23) and SNOT-22 score of 41 (19). Conclusion Broader consideration of initially available clinical data may improve diagnostic efficiency for rhinologic conditions without ancillary studies, using computer-driven algorithms. PRQOL scores and demographic information appeared to be useful adjuncts, with associations to diagnoses in this pilot study.
Cost-effectiveness of dapagliflozin in chronic heart failure: an analysis from the Australian healthcare perspective
Authors: Savira Feby , Wang Bing H , Kompa Andrew R , Ademi Zanfina , Owen Alice J , Zoungas Sophia , Tonkin Andrew , Liew Danny , Zomer Ella 
Published: July 2020

Abstract

Aim
To assess the cost-effectiveness of dapagliflozin in addition to standard care versus standard care alone in patients with chronic heart failure and reduced ejection fraction.

Methods
A Markov model was constructed based on the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure trial to assess the clinical outcomes and costs of 1000 hypothetical subjects with established heart failure and reduced ejection fraction. The model consisted of three health states: ‘alive and event-free’, ‘alive after non-fatal hospitalisation for heart failure’ and ‘dead’. Costs and utilities were estimated from published sources. The main outcome was the incremental cost-effectiveness ratio per quality-adjusted life-year gained. An Australian public healthcare perspective was employed. All outcomes and costs were discounted at a rate of 5% annually.

Results
Over a lifetime horizon, the addition of dapagliflozin to standard care in patients with heart failure and reduced ejection fraction prevented 88 acute heart failure hospitalisations (including readmissions) and yielded an additional 416 years of life and 288 quality-adjusted life-years (discounted) at an additional cost of A$3,692,440 (discounted). This equated to an incremental cost-effectiveness ratio of A$12,482 per quality-adjusted life-year gained, well below the Australian willingness-to-pay threshold of A$50,000 per quality-adjusted life-year gained. Subanalyses in subjects with and without diabetes resulted in similar incremental cost-effectiveness ratios of A$13,234 and A$12,386 per quality-adjusted life-year gained, respectively.

Conclusion
Dapagliflozin is likely to be cost-effective when used as an adjunct therapy to standard care compared with standard care alone for the treatment of chronic heart failure and reduced ejection fraction.
Does finasteride treatment for benign prostatic hyperplasia influence sperm DNA integrity in dogs?
Authors: Angrimani Daniel S. R. , Bicudo Luana C. , Llamas Luceño Nuria , Rui Bruno R. , Silva Matheus F. , Losano João D. A. , Leemans Bart , Van Soom Ann , Vannucchi Camila I. 
Published: July 2020

Abstract
Background
Benign prostatic hyperplasia (BPH) is one of the most common reproductive disorders in both male dogs and men. Finasteride, a synthetic inhibitor of the enzyme 5α-reductase, is widely used as medical treatment. Although sperm can be affected by both BPH and finasteride treatment, the direct influence on DNA integrity remains unclear. Thus, the aim of this study was to verify the direct effect of BPH and/or finasteride treatment on DNA integrity of dog spermatozoa. A 2 × 2 factorial experiment was designed with 20 male dogs assigned to 4 experimental groups: BPH Group (n = 5), BPH-Finasteride Group (n = 5), Non-BPH Finasteride-Treated Group (n = 5) and Non-BPH Untreated Group (n = 5). Sperm evaluation was performed monthly for 60 days after the start of finasteride therapy or BPH diagnosis (D0, D30 and D60). Sperm DNA integrity was analyzed through fragmentation susceptibility (toluidine blue staining and Sperm Chromatic Structure Assay - SCSA), direct evaluation of DNA fragmentation (Sperm Chromatin Dispersion Assay - SCDA) and sperm protamination (chromomycin A3).

Results
Sperm DNA integrity was not affected by finasteride treatment. However, BPH dogs had higher susceptibility to sperm DNA acid denaturation (SCSA) compared to dogs not presenting BPH, as well as lower percentage of sperm with DNA integrity (toluidine blue staining).

Conclusion
In conclusion, benign prostatic hyperplasia causes post-testicular sperm DNA damage, albeit finasteride treatment itself does not directly influence sperm DNA integrity.
Knockdown of DEPDC1B inhibits the development of glioblastoma
Authors: Chen Xu , Guo Zheng-Qian , Cao Dan , Chen Yong , Chen Jian 
Published: July 2020

Abstract
Background
Glioblastoma (GBM) is the most common primary malignant brain tumor in adults with a poor prognosis. DEPDC1B (DEP domain-containing protein 1B) has been shown to be associated with some types of malignancies. However, the role and underlying regulatory mechanisms of DEPDC1B in GBM remain elusive.

Methods
In this research, the expression level of DEPDC1B in GBM tissues was detected by IHC. The DEPDC1B knockdown cell line was constructed, identified by qRT-PCR and western blot and used to construct the xenotransplantation mice model and intracranial xenograft model. MTT assay, colony formation assay, flow cytometry, and Transwell assay were used to detected cell proliferation, apoptosis and migration.

Results
The results proved that DEPDC1B was significantly upregulated in tumor tissues, and silencing DEPDC1B could inhibit proliferation, migration and promote apoptosis of GBM cell. In addition, human apoptosis antibody array detection showed that after DEPDC1B knockdown, the expression of apoptosis-related proteins was downregulated, such as IGFBP-2, Survivin, N-cadherin, Vimentin and Snail. Finally, we indicated that knockdown of DEPDC1B significantly inhibited tumor growth in vivo.

Conclusions
In summary, DEPDC1B was involved in the development and progression of GBM, which may be a potential therapeutic target and bring a breakthrough in the treatment.
Screening and verification of long noncoding RNA promoter methylation sites in hepatocellular carcinoma
Authors: Lin Zhuo , Ni Xiaofeng , Dai Shengjie , Chen Hao , Chen Jianhui , Wu Boda , Ao Jianyang , Shi Keqing , Sun Hongwei 
Published: July 2020

Abstract
Background
Long noncoding ribonucleic acid (lncRNA) promoter methylation is closely related to the occurrence and development of hepatocellular carcinoma (HCC). Thus, we aim to screen and verify the lncRNA promoter methylation sites associated with overall survival (OS), vascular invasion, pathological grade, and clinical stage in HCC.

Methods
Methylation-related data including clinical characteristic, transcriptome, methylation, and messenger RNA (mRNA) expression were taken from the Cancer Genome Atlas (TCGA) database. The OS, vascular invasion, pathological grade, and clinical stage-related lncRNA promoter methylation models were developed by the least absolute shrinkage and selection operator (LASSO) algorithm based on the lncRNA promoter methylation sites screened via R software. The Kaplan–Meier analysis, the area under the receiver operating characteristic (ROC) curve (AUC), the calibration curve (C-index) were performed to evaluate the performance of these models. Finally, the methylation-specific polymerase chain reaction (MS-PCR) was performed to verify the accuracy of these models based on 146 HCC tissues from our hospital.

Results
A total of 10 methylation sites were included in the OS-related lncRNA promoter methylation model that could effectively divide HCC patients into high-risk and low-risk groups (P < 0.0001) via survival analysis. COX univariable and multivariable regression analysis found that the OS-related model (P < 0.001, 95% CI 1.378–2.942) and T stage (P < 0.001, 95% CI 1.490–3.418) were independent risk factors affecting OS in HCC patients. The vascular invasion-related model contained 8 methylation sites with its AUC value of 0.657; the pathological grade-related model contained 22 methylation sites with its AUC value of 0.797; the clinical stage-related model contained 13 methylation sites with its AUC of 0.724. Target genes corresponded to vascular invasion-related lncRNA promoter methylation sites were involved in many kinds of biological processes in HCC such as PI3K-Akt signaling pathway. The accuracy of the vascular invasion-related model was consistent with our bioinformatics conclusion after being verified via MS-PCR.

Conclusion
The lncRNA promoter methylation sites are closely correlated with the process of HCC and can be utilized to improve the therapy and prognosis of HCC.
A novel LncRNA transcript, RBAT1, accelerates tumorigenesis through interacting with HNRNPL and cis-activating E2F3
Authors: He Xiaoyu , Chai Peiwei , Li Fang , Zhang Leilei , Zhou Chuandi , Yuan Xiaoling , Li Yongyun , Yang Jie , Luo Yingxiu , Ge Shengfang , Zhang He , Jia Renbing , Fan Xianqun 
Published: July 2020

AbstractBackgroundLong non-coding RNAs (lncRNAs) have been identified as important epigenetic regulators that play critical roles in human cancers. However, the regulatory functions of lncRNAs in tumorigenesis remains to be elucidated. Here, we aimed to investigate the molecular mechanisms and potential clinical application of a novel lncRNA, retinoblastoma associated transcript-1 (RBAT1), in tumorigenesis.MethodsRBAT1 expression was determined by real-time PCR in both retinoblastoma (Rb) and bladder cancer (BCa) cell lines and clinical tissues. Chromatin isolation using RNA purification (ChIRP) assays were performed to identify RBAT1-interacting proteins. Patient-derived xenograft (PDX) retinoblastoma models were established to test the therapeutic potential of RBAT1-targeting GapmeRs.ResultsHere, we found that RBAT1 expression was significantly higher in Rb and BCa tissues than that in adjacent tissues. Functional assays revealed that RBAT1 accelerated tumorigenesis both in vitro and in vivo.Mechanistically, RBAT1 recruited HNRNPL protein to E2F3 promoter, thereby activating E2F3 transcription. Therapeutically, GapmeR-mediated RBAT1 silencing significantly inhibited tumorigenesis in orthotopic xenograft retinoblastoma models derived from Rb cell lines and Rb primary cells.ConclusionsRBAT1 overexpression upregulates a known oncogene, E2F3, via directly recruiting HNPNPL to its promoter and cis-activating its expression. Our finding provides a novel mechanism of lncRNA biology and provides potential targets for diagnosis and treatment of Rb and BCa.
Single-cell lineage analysis reveals genetic and epigenetic interplay in glioblastoma drug resistance
Authors: Eyler Christine E. , Matsunaga Hironori , Hovestadt Volker , Vantine Samantha J. , van Galen Peter , Bernstein Bradley E. 
Published: July 2020

Abstract
Background
Tumors can evolve and adapt to therapeutic pressure by acquiring genetic and epigenetic alterations that may be transient or stable. A precise understanding of how such events contribute to intratumoral heterogeneity, dynamic subpopulations, and overall tumor fitness will require experimental approaches to prospectively label, track, and characterize resistant or otherwise adaptive populations at the single-cell level. In glioblastoma, poor efficacy of receptor tyrosine kinase (RTK) therapies has been alternatively ascribed to genetic heterogeneity or to epigenetic transitions that circumvent signaling blockade.

Results
We combine cell lineage barcoding and single-cell transcriptomics to trace the emergence of drug resistance in stem-like glioblastoma cells treated with RTK inhibitors. Whereas a broad variety of barcoded lineages adopt a Notch-dependent persister phenotype that sustains them through early drug exposure, rare subclones acquire genetic changes that enable their rapid outgrowth over time. Single-cell analyses reveal that these genetic subclones gain copy number amplifications of the insulin receptor substrate-1 and substrate-2 (IRS1 or IRS2) loci, which activate insulin and AKT signaling programs. Persister-like cells and genomic amplifications of IRS2 and other loci are evident in primary glioblastomas and may underlie the inefficacy of targeted therapies in this disease.

Conclusions
A method for combined lineage tracing and scRNA-seq reveals the interplay between complementary genetic and epigenetic mechanisms of resistance in a heterogeneous glioblastoma tumor model.
Effects of Supervised Early Resistance Training versus standard care on cognitive recovery following cardiac surgery via median sternotomy (the SEcReT study): protocol for a randomised controlled pilot study
Authors: Pengelly Jacqueline M. S. , Royse Alistair G. , Bryant Adam L. , Williams Gavin P. , Tivendale Lynda J. , Dettmann Timothy J. , Canty David J. , Royse Colin F. , El-Ansary Doa A. 
Published: July 2020

Abstract
Introduction
Mild cognitive impairment is considered a precursor to dementia and significantly impacts upon quality of life. The prevalence of mild cognitive impairment is higher in the post-surgical cardiac population than in the general population, with older age and comorbidities further increasing the risk of cognitive decline. Exercise improves neurogenesis, synaptic plasticity and inflammatory and neurotrophic factor pathways, which may help to augment the effects of cognitive decline. However, the effects of resistance training on cognitive, functional and overall patient-reported recovery have not been investigated in the surgical cardiac population. This study aims to determine the effect of early moderate-intensity resistance training, compared to standard care, on cognitive recovery following cardiac surgery via a median sternotomy. The safety, feasibility and effect on functional recovery will also be examined.

Methods
This study will be a prospective, pragmatic, pilot randomised controlled trial comparing a standard care group (low-intensity aerobic exercise) and a moderate-intensity resistance training group. Participants aged 18 years and older with coronary artery and/or valve disease requiring surgical intervention will be recruited pre-operatively and randomised 1:1 to either the resistance training or standard care group post-operatively. The primary outcome, cognitive function, will be assessed using the Alzheimer’s Disease Assessment Scale and cognitive subscale. Secondary measures include safety, feasibility, muscular strength, physical function, multiple-domain quality of recovery, dynamic balance and patient satisfaction. Assessments will be conducted at baseline (pre-operatively) and post-operatively at 2 weeks, 8 weeks, 14 weeks and 6 months.

Discussion
The results of this pilot study will be used to determine the feasibility of a future large-scale randomised controlled trial that promotes the integration of early resistance training into existing aerobic-based cardiac rehabilitation programs in Australia.

Trial registration
Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12617001430325p. Registered on 9 October 2017. Universal Trial Number (UTN): U1111-1203-2131.