bluuebunny/crossref_metadata_2025_split huggingface dataset:
A mixed methodology, non-interventional study to evaluate the use of direct oral anticoagulants in UK clinical practice for patients with a first stroke associated with non-valvular atrial fibrillation: study protocol
Authors: Bhat Yaqoob , Dixit Anand , Mistri Amit , Patel Bhavini , Quoraishi Sadat Haider , Uprichard James 
Published: November 2019

Abstract
Background
Treatment with anticoagulants, including direct oral anticoagulants (DOACs), should be considered for patients diagnosed with atrial fibrillation (AF) deemed at risk of ischaemic stroke. There are limited real world data related to the characteristics of patients with non-valvular AF who were not taking anticoagulants at the time of first ischaemic stroke and their subsequent DOAC treatment for the secondary prevention of stroke. Furthermore, little is known about patient adherence and experiences of DOAC treatment, especially for patients with non-valvular AF receiving DOAC therapy for the secondary prevention of stroke.

Methods
This is a UK mixed methodology, non-interventional study, involving retrospective and prospective medical record reviews and a prospective patient survey, in progress in six UK National Health Service secondary/tertiary care centres. The study comprises two groups of patients. Group 1 will include 300 eligible consenting patients with a first ischaemic stroke associated with non-valvular AF untreated with anticoagulants in the 12 months prior to stroke. Group 2 will include a subgroup of 150 patients from Group 1 initiated on one of the DOACs targeting activated Factor X (n = 50 on apixaban, n = 50 on edoxaban and n = 50 on rivaroxaban). The primary endpoint of the study is the CHA2DS2-VASc Risk Score prior to initiation of anticoagulation for patients included in Group 1. Secondary endpoints to be evaluated in Group 1 include patient demographics, clinical characteristics, relevant medical history, anticoagulant therapy initiated for secondary prevention of stroke, and relevant concomitant medication. Secondary endpoints to be evaluated in Group 2 include the time between stroke and DOAC initiation; prescribing of DOACs, other anticoagulants and concomitant medication; clinical assessments and hospital resource use; patient reported outcome measures, including the Morisky Medication Adherence Scale questionnaire and the Treatment Satisfaction Questionnaire for Medication.

Discussion
This mixed methodology study will provide new real world insights into the characteristics and management pathways and patient-reported experiences of this important group of patients. It is anticipated that the results of this study will provide the medical community and patients with important information to inform clinical decision-making and help facilitate meaningful improvements in the care of patients with non-valvular AF.
MPPa-PDT suppresses breast tumor migration/invasion by inhibiting Akt-NF-κB-dependent MMP-9 expression via ROS
Authors: Huang Liyi , Lin Haidan , Chen Qing , Yu Lehua , Bai Dingqun 
Published: November 2019

Abstract
Background
Breast cancer is one of the most commonly diagnosed cancers in women, with high morbidity and mortality. Tumor metastasis is implicated in most breast cancer deaths; thus, inhibiting metastasis may provide a therapeutic direction for breast cancer. In the present study, pyropheophorbide-α methyl ester-mediated photodynamic therapy (MPPa-PDT) was used to inhibit metastasis in MCF-7 breast cancer cells.

Methods
Uptake of MPPa was detected by fluorescence microscopy. Cell viability was evaluated by the Cell Counting Kit-8 (CCK-8). ROS generation was detected by 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA). The migration of cells was assessed by wound healing assay, and invasion ability was assessed by Matrigel invasion assay. Levels of MMP2 and MMP9 were measured by PCR. Akt, phospho-Akt (Ser473), phospho-NF-κB p65 (Ser536) and NF-κB p65 were measured by western blotting. The F-actin cytoskeleton was observed by immunofluorescence. Lung tissue was visualized by hematoxylin and eosin staining.

Results
Following MPPa-PDT, migration and invasion were decreased in the MCF-7 cells. MPPa-PDT downregulated the expression of MMP2 and MMP9, which are responsible for the initiation of metastasis. MPPa-PDT reduced the phosphorylation of Akt and NF-κB. MPPa-PDT also reduced the expression of F-actin in cytoskeleton in MCF-7 cells. These effects were blocked by the reactive oxygen species scavenger NAC or the Akt activator SC79, while the PI3K inhibitor LY294002 or the Akt inhibitor triciribine enhanced these effects. Moreover, MPPa-PDT inhibited tumor metastasis and destroyed F-actin in vivo.

Conclusion
Taken together, these results demonstrate that MPPa-PDT inhibits the metastasis of MCF-7 cells both in vitro and in vivo and may be involved in the Akt/NF-κB-dependent MMP-9 signaling pathway. Thus, MPPa-PDT may be a promising treatment to inhibit metastasis.
RETRACTED ARTICLE: Syndecan-1 suppresses cell growth and migration via blocking JAK1/STAT3 and Ras/Raf/MEK/ERK pathways in human colorectal carcinoma cells
Authors: Wang Shaojun , Zhang Xiaofei , Wang Guimei , Cao Bin , Yang Hong , Jin Lipeng , Cui Mingjuan , Mao Yongjun 
Published: November 2019

Abstract
Background
Syndecan-1 (SDC-1) is a crucial membrane proteoglycan, which is confirmed to participate in several tumor cell biological processes. However, the biological significance of SDC-1 in colorectal carcinoma is not yet clear. An objective of this study was to investigate the role of SDC-1 in colorectal carcinoma cells.

Methods
Expression of SDC-1 in colorectal carcinoma tissues was evaluated by Reverse transcription-quantitative real-time PCR (RT-qPCR) and western blot. After transfection with pcDNA3.1 or pc-SDC-1, the transfection efficiency was measured. Next, SW480, SW620 and LOVO cell viability, apoptosis, migration and adhesion were assessed to explore the effects of exogenous overexpressed SDC-1 on colorectal carcinoma. In addition, the influences of aberrant expressed SDC-1 in Janus kinase 1 (JAK1)/signal transducer and activator of transcription 3 (STAT3) and rat sarcoma virus (Ras)/rapidly accelerated fibrosarcoma (Raf)/mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) pathways were detected by western blot analysis.

Results
SDC-1 mRNA and protein levels were down-regulated in human colorectal carcinoma tissues. SDC-1 overexpression inhibited cell proliferation via suppressing CyclinD1 and c-Myc expression, meanwhile stimulated cell apoptosis via increasing the expression levels of B-cell lymphoma-2-associated x (Bax) and Cleaved-Caspase-3. Additionally, SDC-1 overexpression restrained cell migration via inhibiting the protein expression of matrix metallopeptidase 9 (MMP-9), and elicited cell adhesion through increasing intercellular cell adhesion molecule-1 (ICAM-1). Furthermore, SDC-1 overexpression suppressed JAK1/STAT3 and Ras/Raf/MEK/ERK-related protein levels.

Conclusions
In general, the evidence from this study suggested that SDC-1 suppressed cell growth, migration through blocking JAK1/STAT3 and Ras/Raf/MEK/ERK pathways in human colorectal carcinoma cells.
Radiotherapy for metastatic spinal cord compression with increased radiation doses (RAMSES-01): a prospective multicenter study
Authors: Rades Dirk , Hansen Olfred , Jensen Lars Henrik , Dziggel Liesa , Staackmann Christian , Doemer Claudia , Cacicedo Jon , Conde-Moreno Antonio J. , Segedin Barbara , Ciervide-Jurio Raquel , Rubio-Rodriguez Carmen , Perez-Romasanta Luis A. , Alvarez-Gracia Ana , Dennis Kristopher , Ferrer-Albiach Carlos , Navarro-Martin Arturo , Lopez-Campos Fernando , Jankarashvili Natalia , Janssen Stefan , Olbrich Denise , Holländer Niels Henrik 
Published: November 2019

Abstract
Background
Patients with metastatic spinal cord compression (MSCC) and favorable survival prognoses can benefit from radiation doses greater than 30Gy in 10 fractions in terms of improved local progression-free survival (LPFS) and overall survival (OS).

Methods/design
This prospective study mainly investigates LPFS after precision radiotherapy (volumetric modulated arc therapy or stereotactic body radiotherapy) with 18 × 2.33Gy in 3.5 weeks. LPFS is defined as freedom from progression of motor deficits during radiotherapy and an in-field recurrence of MSCC following radiotherapy. The maximum relative dose allowed to the spinal cord is 101.5% of the prescribed dose, resulting in an equivalent dose in 2Gy-fractions (EQD2) for radiation myelopathy is 45.5Gy, which is below the tolerance dose of 50Gy according to the Quantitative Analyses of Normal Tissue Effects in the Clinic (QUANTEC). The EQD2 of this regimen for tumor cell kill is 43.1Gy, which is 33% higher than for 30Gy in 10 fractions (EQD2 = 32.5Gy). Primary endpoint is LPFS at 12 months after radiotherapy. Secondary endpoints include the effect of 18 × 2.33Gy on motor function, ambulatory status, sensory function, sphincter dysfunction, LPFS at other follow-up times, overall survival, pain relief, relief of distress and toxicity. Follow-up visits for all endpoints will be performed directly and at 1, 3, 6, 9 and 12 months after radiotherapy. A total of 65 patients are required for the prospective part of the study. These patients will be compared to a historical control group of at least 235 patients receiving conventional radiotherapy with 10x3Gy in 2 weeks.

Discussion
If precision radiotherapy with 18 × 2.33Gy results in significantly better LPFS than 10x3Gy of conventional radiotherapy, this regimen should be strongly considered for patients with MSCC and favorable survival prognoses.

Trial registration
Clinicaltrials.gov NCT04043156. Registered 30-07-2019.
Liver stiffness measurement predicts the difficulty of Kasai procedure in biliary atresia: a single center retrospective analysis of 199 patients
Authors: Shen Qiulong , Chen Yajun , Peng Chunhui , Pang Wenbo , Wang Zengmeng , Wu Dongyang , Wang Kai , Huang Xinjie 
Published: November 2019

Abstract
Background
Kasai procedure is the standard initial treatment of infants with biliary atresia. The key to perform a successful surgery is to accurately remove the fibrous portal plate near the liver hilum. Yet how to estimate surgical difficulty pre-operatively remains unclear. This study aims to design an algorithm that predicts the difficulty of Kasai procedure using liver stiffness measurement (LSM).

Methods
One hundred ninety-nine patients were included from April 2012 to December 2016. The patients were all surgically diagnosed with biliary atresia. Group A comprised of patients with porta hepatis retraction (the angle between the plane of the fibrous porta plate and the plane of the medial liver closest to the plate was equal to or smaller than 90°), group B comprised of patients without porta hepatis retraction (the angle between the plane of the fibrous porta plate and the plane of the medial liver closest to the plate was greater than 90°). Liver function measurements and LSM were measured for all patients within three days before surgery.

Results
Our study included 19 cases in group A (9 males, 10 females) and 180 cases in group B (87 males, 93 females). LSM had statistical differences between the two groups, 28.10(14.90) kPa VS 10.89(7.10) kPa, P = 0.000. There was a significant relationship between LSM and operative age, TBA, AST, GGT (P = 0.000, 0.003, 0.003, 0.012, correlation coefficient = 0.323, 0.213, 0.207, 0.179). The AUROC of LSM was 0.919. When the cutoff value was 15.15 kPa(OR = 3.989; P = 0.000), the sensitivity, specificity, PPV, NPV and diagnostic accuracy were 0.947, 0.750, 0.285, 0.992 and 0.768, respectively. When the value was 23.75 kPa(OR = 3.483; P = 0.000), the sensitivity, specificity, PPV, NPV and diagnostic accuracy were 0.631, 0.950, 0.571, 0.960 and 0.919, respectively.

Conclusions
LSM can be used to predict the difficulty in dissecting fibrous portal plate, and in turn, the difficulty of Kasai procedure. LSM > 23.75 kPa suggests a more complicated surgery.
Implicit affectivity in clinically depressed patients during acute illness and recovery
Authors: Suslow Thomas , Bodenschatz Charlott Maria , Kersting Anette , Quirin Markus , Günther Vivien 
Published: November 2019

Abstract
Background
Clinical depression is characterized by high levels of negative affect (NA) and attenuated positive affect (PA). Psychological and pharmacological treatments have been shown to reduce NA and to enhance PA in depressed patients. Following dual-process models, two types of affect can be distinguished: explicit (or self-reported) affect, which is formed by conscious reflections, and implicit affect, which relates to automatic affective reactions. The present study was conducted to examine, for the first time, both implicit and explicit affectivity in patients suffering from acute depression. Moreover, changes in patients’ implicit and explicit affectivity were investigated over the course of inpatient treatment.

Methods
Thirty-nine patients suffering from major depression and 39 healthy individuals participated in the study. Implicit affectivity was assessed using the Implicit Positive and Negative Affect Test. The explicit state and trait affectivity were measured by the Positive and Negative Affect Schedule. The level of depressive symptoms was assessed with the Beck Depression Inventory. Tests were administered to patients after admission and after 7 weeks of therapy, whereas healthy controls were investigated only once. We examined whether either comorbidity or antidepressant medication has an effect on affectivity.

Results
Patients with acute depression had lower implicit and explicit PA scores and higher implicit and explicit NA scores than the healthy controls. After treatment, patients’ level of depression decreased significantly. At posttreatment, patients exhibited heightened implicit and explicit PA and diminished explicit trait NA. Independent of antidepressant medication and comorbidity, no significant change in implicit NA was observed over the course of treatment. Implicit NA was correlated with explicit NA in acute depression but not during recovery.

Conclusions
Acute depression appears to be characterized by decreased implicit and explicit PA and increased implicit and explicit NA. After 7 weeks of treatment, depressed patients’ implicit and explicit PA increased, and explicit trait NA decreased. No decrease in implicit NA and explicit state NA occurred over the course of treatment. Finally, it seems that in the state of acute depression, the interplay between the automatic and reflective systems could be increased for negative affectivity.
Development of a community-based hearing loss prevention and control service model in Guangdong, China
Authors: Liu Chang , Wang Anshi , Huang Yanlin , Zhang Yan , Ding Hongke , Wu Jing , Du Li , Yang Jie , Mai Fei , Zeng Yukun , Liu Ling , Zhao Xin , Zhang Changbin , Yin Aihua 
Published: November 2019

Abstract
Background
Hearing loss is a prevalent sensorineural disorder and a major public health issue in China. It is suggested that half of all cases of hearing loss can be prevented through public health measures. However, national strategies for hearing healthcare are not implemented well in Guangdong and some other regions in China.

Methods
To develop a community-based service model for the prevention and control of hearing loss in Guangdong, we integrated the model with multiple maternal and child healthcare models, and set up a series of clinical programs along with an optimum timeline for the preventive measures and intervention treatments to take place. A total of 36,090 families were enrolled in the study, including 358 high-risk families and 35,732 general-risk families.

Results
The study lasted for 6.5 years, and 30,769 children were born during that period. A total of 42 children were born with congenital deafness; 17 of them were born into families with advanced genetic risks for hearing loss, 9 were born with specific medical conditions, and 16 were born into general-risk families. About one third of them were diagnosed prenatally, others were diagnosed within 3 months of age, and 72% of them received interventions initiated before 6 months of age. 13 children presented with delayed hearing loss; 9 of them were diagnosed with delayed hereditary sensorineural deafness in neonatal period, and 4 were diagnosed within 3 months after onset. Timely interventions were provided to them, with appropriate referrals and follow-ups. Beside these, 80 families were identified with genetic susceptibility to aminoglycoside ototoxicity. Detailed medication guides were provided to prevent aminoglycoside-induced hearing loss. Moreover, through health education and risk reduction strategies, the prevalence of TORCH syndrome decreased from 10.7 to 5.2 per 10,000. Additionaly, the awareness rates of health knowledge about hearing healthcare significantly increased in the cohort.

Conclusions
Adapting national strategies for local or district projects could be an important step in implementing hearing loss prevention measures, and developing community-based service models could be of importance in carrying them out.
Knowledge on the action to be taken and recognition of symptoms of stroke in a community: findings from the May Measurement Month 2017 blood pressure screening Programme in Malaysia
Authors: Ching SiewMooi , Chia Yook Chin , Chew Bee Nah , Soo Man Jun , Lim Hooi Min , Sulaiman Wan Aliaa Wan , Hoo Fan Kee , Saw Mar Lar , Ishak Azlina , Palanivelu Tharmalingam , Caruppaiya Nadarajan , Devaraj Navin Kumar 
Published: November 2019

Abstract
Background
Information regarding the knowledge on the action to be taken during stroke and good recognition of stroke symptoms is mandatory in helping to plan out educational strategies to deliver health education to the community.

Methods
This is a cross-sectional study of adults aged 18 and above attending a blood pressure screening program in community in conjunction with May Measurement Month 2017 in Malaysia. A structured self-administered questionnaire was given to the participants who gave verbal consent. Data analysis was done using SPSS v. 23 and multiple logistic regression was used to identify the determinants of knowledge on actions to be taken during stroke and recognition of stroke symptoms.

Results
Out of 4096 respondents, 82.9–92.1% of them able to recognise the common stroke symptoms. and 74.2% of the study respondents will go to hospital within 4.5 h of stroke onset. According to binomial logistic regression analyses, adults aged 45 years old and above (OR 1.39 95%CI 1.01–1.92), being Malay (OR 1.74, 95% CI 1.27–2.40), being non-smokers (OR = 2.491, 95% CI: 1.64–3.78), hypertensives (OR: 1.57, 95% CI: 1.02–2.42)and diabetics (OR: 2.54, 95% CI:1.38–4.69) are determinants of right actions to be taken during stroke. Meanwhile, respondents aged 45 years old and older (OR = 1.68, 95% CI: 1.39–2.03), being Malay (OR = 1.49, 95% CI: 1.24–1.79), hypertensive (OR = 1.32, 95% CI: 1.04–1.66) and those who had a previous history of stroke (OR = 2.25, 95% CI: 1.01–5.00) are determinants of good recognition of stroke symptoms.

Conclusions
The overall knowledge of stroke in our study population was good. Older age, being Malay, non-smokers, hypertensives and diabetics are determinants of right actions to be taken during stroke. Meanwhile, older age, being Malay, hypertensive and those who had a previous history of stroke are determinants of good recognition of stroke symptoms.
Protocol for a cluster randomised control trial evaluating the efficacy and safety of treatment for latent tuberculosis infection in recent migrants within primary care: the CATAPuLT trial
Authors: Burman M. , Copas A. , Zenner D. , Hickson V. , Gosce L. , Trathen D. , Ashcroft R. , Martineau A. R. , Abubakar I. , Griffiths C. , Kunst H. 
Published: November 2019

Abstract
Background
The identification and treatment of LTBI is a key component of the WHO’s strategy to eliminate TB. Recent migrants from high TB-incidence countries are recognised to be at risk TB reactivation, and many high-income countries have focused on LTBI screening and treatment programmes for this group. However, migrants are the group least likely to complete the LTBI cascade-of-care. This pragmatic cluster-randomised, parallel group, superiority trial investigates whether a model of care based entirely within a community setting (primary care) will improve treatment completion compared with treatment in specialist TB services (secondary care).

Methods
The CATAPuLT trial (Completion and Acceptability of Treatment Across Primary Care and the community for Latent Tuberculosis) randomised 34 general practices in London, England, to evaluate the efficacy and safety of treatment for LBTI in recent migrants within primary care. GP practices were randomised to either provide management for LTBI entirely within primary care (GPs and community pharmacists) or to refer patients to secondary care. The target recruitment number for individuals is 576. The primary outcome is treatment completion (defined as taking at least 90% of antibiotic doses). The secondary outcomes assess adherence, acceptance of treatment, the incidence of adverse effects including drug-induced liver injury, the rates of active TB, patient satisfaction and cost-effectiveness of LTBI treatment. This protocol adheres to the SPIRIT Checklist.

Discussion
The CATAPuLT trial seeks to provide implementation research evidence for a patient-centred intervention to improve treatment completion for LTBI amongst recent migrants to the UK.

Trial registration
NCT03069807, March 2017, registered retrospectively.
Prognostic value of cardiopulmonary exercise testing in patients with systemic sclerosis
Authors: Ewert Ralf , Ittermann Till , Habedank Dirk , Held Matthias , Lange Tobias J. , Halank Michael , Winkler Jörg , Gläser Sven , Olschewski Horst , Kovacs Gabor 
Published: November 2019

Abstract
Background
Systemic sclerosis (SSc) is a severe rheumatic disease of the interstitial tissue, in which heart and lung involvement can lead to disease-specific mortality. Our study tests the hypothesis that in addition to established prognostic factors, cardiopulmonary exercise testing (CPET) parameters, particularly peak oxygen uptake (peakVO2) and ventilation/carbon dioxide (VE/VCO2)-slope, can predict survival in patients with SSc.

Subjects and methods
We retrospectively assessed 210 patients (80.9% female) in 6 centres over 10 years with pulmonary testing and CPET. Survival was analysed with Cox regression analysis (adjusted for age and gender) by age, comorbidity (Charlson-Index), body weight, body-mass index, extensive interstitial lung disease, pulmonary artery pressure (measured by echocardiography and invasively), and haemodynamic, pulmonary and CPET parameters.

Results
Five- and ten-year survival of SSc patients was 93.8 and 86.9%, respectively. There was no difference in survival between patients with diffuse (dcSSc) and limited cutaneous manifestation (lcSSc; p = 0.3). Pulmonary and CPET parameters were significantly impaired. Prognosis was worst for patients with pulmonary hypertension (p = 0.007), 6-min walking distance < 413 m (p = 0.003), peakVO2 < 15.6 mL∙kg− 1∙min− 1, and VE/VCO2-slope > 35. Age (hazard ratio HR = 1.23; 95% confidence interval CI: 1.14;1.41), VE/VCO2-slope (HR = 0.9; CI 0.82;0.98), diffusion capacity (Krogh factor, HR = 0.92; CI 0.86;0.98), forced vital capacity (FVC, HR = 0.91; CI 0.86;0.96), and peakVO2 (HR = 0.87; CI 0.81;0.94) were significantly linked to survival in multivariate analyses (Harrell’s C = 0.95).

Summary
This is the first large study with SSc patients that demonstrates the prognostic value of peakVO2 < 15.6 mL∙kg− 1∙min− 1 (< 64.5% of predicted peakVO2) and VE/VCO2-slope > 35.