bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dual effect of the Valsalva maneuver on autonomic nervous system activity, intraocular pressure, Schlemm’s canal, and iridocorneal angle morphology
Authors: Sun Li , Chen Wei , Chen Zhiqi , Xiang Yan , Guo Jingmin , Hu Tian , Xu Qiongfang , Zhang Hong , Wang Junming 
Published: July 2019

Abstract
Background

The Valsalva maneuver (VM) is common in the daily life and has been reported to cause high intraocular pressure (IOP). This study aimed to assess changes in IOP, Schlemm’s canal (SC), autonomic nervous system activity and iridocorneal angle morphology in healthy individuals during different phases of the VM.

Methods

The high frequency (HF) of heart rate variability (HRV), the ratio of low frequency power and high frequency power (LF/HF), heart rate (HR), IOP, systolic (SBP) and diastolic blood pressure (DBP), the area of Schlemm’s canal (SCAR), pupil diameter (PD) and some iridocorneal angle parameters (AOD500, ARA750, TIA500 and TISA500) were measured in 29 young healthy individuals at baseline, phase 2 and phase 4 of the VM. SBP and DBP were measured to calculate mean arterial pressure (MAP) and mean ocular perfusion pressure (MOPP). HF and LF/HF ratio were recorded using Kubios HRV Premium software to evaluate autonomic nervous activity. The profiles of anterior chamber were captured by a Spectralis optical coherence tomography device (anterior segment module).

Results

Compared with baseline values, in phase 2 of the VM, HR, LF/HF, IOP (15.1 ± 2.7 vs. 18.8 ± 3.5 mmHg, p < 0.001), SCAR(mean) (7448.64 ± 3230.82 vs. 8851.43 ± 4231.15 μm2, p = 0.038) and PD increased significantly, whereas MOPP, AOD500, ARA750, TIA500 and TISA500 decreased significantly. In phase 4, HR, DBP, MAP, MOPP, AOD500, ARA750, TIA500and TISA500 were significantly lower than baseline value, while PD and HF were remarkably larger than baseline. The comparison between phase 2 and phase 4 showed that HR, IOP (19.1 ± 3.3 vs. 14.7 ± 2.9 mmHg, p < 0.001) and PD decreased significantly from phase 2 to phase 4, but there were no significant differences in other parameters.

Conclusions

The expansion and collapse of SC in different phases of the VM may be arise from the changes of autonomic nervous system activity, while its influence on IOP could be counteracted even reversed by the changes of blood flow and ocular anatomy.
Correlation between visual acuity and human leukocyte antigen (HLA)-DRB1*04 in patients with Vogt-Koyanagi-Harada disease
Authors: Misawa Norihiko , Tagami Mizuki , Kohno Takeya , Honda Shigeru 
Published: July 2019

Abstract
Background
Human leukocyte antigen (HLA)-DRB1*04 is well known to be associated with the course of Vogt-Koyanagi-Harada (VKH) disease. The aim of this study was to investigate the relationship between visual prognosis and HLA-DRB1*04 alleles during systemic corticosteroid therapy in patients with VKH disease.

Methods
This retrospective case series included 47 eyes from 29 consecutive treatment-naïve patients who received systemic corticosteroid therapy. Visual acuity sex, refractive error, central retinal thickness (CRT), central choroidal thickness (CCT), and duration from onset to treatment were measured at initial and final visits. Mean values of parameters were compared with each visit. Typing was performed by polymerase chain reaction amplification with sequence-specific primers.

Results
Linear regression showed significant differences in logMAR best-corrected visual acuity among the three groups of homozygotes, heterozygotes, and normal subjects between baseline (p<0.01) and final visit (p=0.012). No significant difference was detected between the three groups in age, sex, refractive error, CRT, CCT, or duration from onset to treatment.

Conclusions
The present study revealed a correlation between HLA04 allele type and visual acuity logMAR before and after initiating systemic corticosteroid therapy in treatment-naïve patients with VKH disease.
Modified regional citrate anticoagulation is optimal for hemodialysis in patients at high risk of bleeding: A prospective randomized study of three anticoagulation strategies
Authors: Lin Ting , Song Li , Huang Renwei , Huang Ying , Tang Shuifu , Lin Qizhan , Zhang Ying , Wu Xingbo , Liang Hui , Wu Yuchi , Chen Yuanhan , Liang Huaban , Ma Jianchao , Feng Zhonglin , Li Zhuo , Xu Lixia , Fu Xia , Ye Zhiming , Liu Shuangxin , Liang Xinling 
Published: July 2019

Abstract
Background：The recommended regular saline flushing presents clinical ineffectiveness for patients at high risk of bleeding with heparin contraindication. Regional citrate anticoagulation (RCA) has been used in a Ca2+ containing dialysate with prefilter citrate in one arm (RCA-one). The anticoagulation effect was not realized, and up to 40% resulted in serious clotting in the venous expansion chamber. We innovatively transferred one-quarter of the TSC from the prefilter to the postfilter based on RCA-one, which is called RCA-two in this trial. The objective of this study was to compare the efficacy and safety of RCA-two with either saline flushing or RCA-one in HD patients with a high bleeding risk. Method：In this investigator-initiated, multicenter, placebo-controlled, prospective, randomized clinical trial, 52 patients (77 sessions) were randomized to the RCA-two and RCA-one group in part one trial, and 45 patients (64 sessions) were randomized to the RCA-two and Saline group in part two trial. Serious clotting events, adverse events and blood analyses were recorded. Results：The primary outcome, Serious clotting events in the RCA-two group were significantly lower than that in the RCA-one and Saline group (7.89% vs. 30.77%, P = 0.011; 3.03% vs. 54.84%, P < 0.001, respectively). The median circuit survival time was 240 min (IQR 240 to 240) in the RCA-two group, which was signiﬁcantly longer than 230 min (IQR 155 to 240, P < 0.001) in the RCA-one group and 210 min (IQR 135 to 240，P = 0.003) in the Saline group. The majority of the AEs were hypotension, hypoglycemia and chest tightness, most of which were mild in intensity. Eight patients (20.51%) in the RCA-one group, 4 patients (12.90%) in the Saline group and 10 patients (26.31%) in the RCA-two group, P>0.05. Conclusions：Our data demonstrated that the modified anticoagulation protocol is more effective and feasible during hemodialysis therapy for patients at high risk of bleeding. Trial registration: GDREC, GDREC2017250H. Registered 2th February 2018-Retrospectively registered.
Keywords: regional citrate anticoagulation, hemodialysis, high risk of bleeding, serious clotting, saline flushing, randomized prospective clinical trial.
The Burden of Unrecognised Chronic Kidney Disease in Patients With Type 2 Diabetes at a County Hospital Clinic in Kenya: Implications to Care and Need for Screening
Authors: Otieno Frederick C. F. , Ogola Elijah N , Kimando Mercy W , Mutai Ken K 
Published: July 2019

Abstract
Background

Chronic Kidney Disease (CKD) in patients with type 2 diabetes enhances the cardiovascular risk profiles and disease, and a strong predictor of progression to end-stage kidney disease. Early diagnosis is encouraged for referral to specialist kidney care to initiate active management that would optimize outcomes including forestalling progression to end-stage kidney disease.

This study was conducted in a regional referral public health facility in Central Kenya with a higher prevalence of type 2 diabetes. It was aimed at finding out the burden of chronic kidney disease in their clinic of ambulatory patients with type 2 diabetes from, mainly, the rural area.

Methods

This was a cross-sectional survey conducted at the out-patient diabetes clinic of Nyeri County hospital. A total of 385 participants with type 2 diabetes were enrolled over five (5) months. Each subject gave informed consent to participate wherein clinical evaluation was done, a spot sample of urine obtained for albuminuria and venous blood drawn for HbA1c, Lipids and serum creatinine. Estimated GFR (eGFR) was calculated using the Cockroft-Gault equation. Chronic kidney disease (CKD) was classified on KDIGO scale. Albuminuria was reported as either positive or negative.

Main outcomes measure

Estimated Glomerular filtration rate and albuminuria as markers of chronic kidney disease.

Results

Of the 385 participants included in the study, 252 (65.5%) were females. Thirty nine per cent, 39.0%(95%CI 34.3-44.2) had CKD/KDIGO stages 3, 4 and 5 while 32.7% (95%CI, 27.8-37.4) had Albuminuria. The risk factors that were significantly associated with chronic kidney disease/KDIGO stages 3, 4 and 5 were: age >50years, long duration with diabetes >5years and hypertension. Employment and, paradoxically, obesity reduced the odds of having CKD, probably as markers of better socio-economic status.

Conclusion

Therefore, patients with type 2 diabetes should be screened for CKD using spot-urine albuminuria and eGFR, then risk-stratified further for cardiovascular disease and likelihood of progression to ESRD. Reducing proteinuria and optimizing control of the modifiable risk factors, especially unawareness, hypertension and hyperglycaemia, by linkage to and retention in quality care is the imperative of screening for chronic kidney disease which is the challenge in publicly-funded hospitals.
Cost containment by peer prior authorization program for second line treatment in patients with retinal disease
Authors: Rosenblatt Amir , Hekselman Igal , Rosenblatt Irit , Hekselman Idan , Gaton Dan 
Published: July 2019

Abstract
Background: Rising drug prices prompt the establishment of cost-containment treatment policies. Ranibizumab was approved for treatment of retinal diseases, although the less-costly, off label, bevacizumab has been found equally effective. We describe a novel prior-authorization approach, which we applied to ranibizumab as second-line treatment, in non-responders to first-line bevacizumab: A steering committee set the funding criteria based on cost and updating clinical considerations; an ophthalmic specialists team evaluated their colleagues’ individual patient subsidization request, based on the funding criteria.
Methods This retrospective cohort included all the applications for a first or ongoing treatment with ranibizumab, for one or both eyes, applying for treatment between March 1, 2012 to December 31, 2015 During that time, 16,778 applications for funding from 5,642 patients (~2.97 applications/patient) were submitted and assessed, accounting for 31% of bevacizumab (first line)-treated patients Aapproval was granted in 94.6% of all requests, via their peer-revision.
Conclusions The program made it feasible to finance a costly treatment for patients that may benefit from it, while maintaining qualitative medical outcomes and sparing treating ophthalmologist from ethical gatekeeping dilemmas
Assessments Used to Measure Participation in Life Activities in Individuals with Cancer: A Scoping Review
Authors: L'Hotta Allison J , Varughese Taniya E. , Lyons Kathleen D. , Simon Laura , King Allison A. 
Published: July 2019

Abstract
Background There is a critical need to facilitate return to work, school, and life activities among individuals with and surviving cancer. Each of these areas is a component of participation, defined by the International Classification of Functioning, Disability, and Health (ICF) as involvement in a life situation. Before developing interventions to address participation, we must first understand how this concept is measured. This scoping review investigates what assessments are currently used to measure participation in life activities in individuals with cancer.
Methods Six databases were systematically searched using keywords and controlled vocabulary through February 2019. Eligible studies used the term participation in the context of life situations and had an assessment with at least 5 participation-specific questions.
Results More than 4,000 references were identified and screened for eligibility. Twenty-seven studies were included; 18 unique assessments of participation were identified. Assessments were 1) developed with the primary purpose of measuring participation (n= 8); 2) measured global or physical function (n=8; 4 had a domain specific to participation); or 3) measured community integration (n=1) or social activity (n=1). Most assessments (10/18) were not developed with the purpose of measuring participation and only 4 assessments measured key components of participation (e.g. satisfaction) other than frequency.
Discussion Measuring participation in life activities is a developing area in oncology research. Most studies do not accurately or comprehensively measure this construct. The heterogeneity in the assessments used indicates no clear consensus on a gold-standard participation measure for use among individuals with cancer. Comprehensively measuring participation is an essential first step to helping individuals with and surviving cancer lead productive and meaningful lives during and after treatment. By identifying deficits in participation, healthcare providers can better understand what activities are most important to their patients and provide necessary interventions. To facilitate the development of targeted interventions, a comprehensive measure of participation needs to be validated for use with individuals with cancer.
ROS as a Novel Indicator to Predict Anticancer Drug Efficacy
Authors: Zaidieh Tarek , Smith James , Ball Karen , An Qian 
Published: July 2019

Abstract
Background

Mitochondria are considered a primary intracellular site of reactive oxygen species (ROS) generation. Generally, cancer cells with mitochondrial genetic abnormalities (copy number change and mutations) have escalated ROS levels compared to normal cells. Since high levels of ROS can trigger apoptosis, treating cancer cells with low doses of mitochondria-targeting / ROS-stimulating agents may offer cancer-specific therapy. This study aimed to investigate how baseline ROS levels might influence cancer cells’ response to ROS-stimulating therapy.

Methods

Four cancer and one normal cell lines were treated with a conventional drug (cisplatin) and a mitochondria-targeting agent (dequalinium chloride hydrate) separately and jointly. Cell viability was assessed and drug combination synergisms were indicated by the combination index (CI). Mitochondrial DNA copy number (MtDNAcn), ROS and mitochondrial membrane potential (MMP) were measured, and the relative expression levels of the genes and proteins involved in ROS-mediated apoptosis pathways were also investigated.

Results

Our data showed a correlation between the baseline ROS level, mtDNAcn and drug sensitivity in the tested cells. Synergistic effect of both drugs was also observed with ROS being the key contributor in cell death.

Conclusions

Our findings suggest that mitochondria-targeting therapy could be more effective compared to conventional treatments. In addition, cancer cells with low levels of ROS may be more sensitive to the treatment, while cells with high levels of ROS may be more resistant. This study provides an insight into understanding the influence of intracellular ROS on drug sensitivity, and may lead to the development of new therapeutic strategies to improve efficacy of anticancer therapy.
Diagnostic value of Telomerase Activity in patients with Bladder cancer: a meta-analysis of diagnostic test
Authors: Peng Lei , He Lujia , Ren ZhengJu , Cao Hong De , Li Jinze , Wei Qiang , Li yunxiang 
Published: July 2019

Abstract
Background

This article aims to evaluate the diagnostic value of telomerase activity (TA) in bladder cancer (BC) by meta-analysis of diagnostic tests.

Methods

We conducted a systematic search of articles published on PubMed, Embase, and Web of Science up to June 1, 2019.Stata 15 and Review Manager 5.3 were used for calculation and statistical analyses.

Results

We use the sensitivity, specificity, positive and negative likelihood ratio (PLR,NLR),diagnostic odds ratio (DOR) and 95% confidengce intervals (CIs) to evaluate the diagnostic value of TA for BC. 22 studies were included in the meta- analyses, with a total of 2867 individuals. The pooled parameters are calculated from all studies: sensitivity of 0.79(95%CI:0.72-0.84), specificity of 0.91(95%CI:0.87-0.94), PLR of 8.91(95%CI:5.91-13.43),NLR of 0.24(95%CI:0.15-0.37), DOR of 37.90(95%CI:23.32-61.59), AUC of 0.92(95%CI:0.90-0.94). We also conducted subgroup based on different stages and grades. Results from subgroup analysis showed that there was no significant difference in TA during the high and low stages BC, but low-grade tumors have lower TA than high-grade tumors.

Conclusions

For the diagnosis of BC, the overall diagnostic value of TA is high, and is expected to be an alternative to cystoscopy for different staging and grading. The tumor also has a very good diagnostic value.
Practical Value of Three-dimensional High Resolution Magnetic Resonance Vessel Wall Imaging in Identifying Suspicious Intracranial Vertebrobasilar Dissecting Aneurysms
Authors: Zhu Xianjin , Qiu Hancheng , Hui Ferdinand K , Zhang Yiqun , Liu Yun-e , Man Fengyuan , Jiang Wei-Jian 
Published: July 2019

Abstract
Background: Direct evidence of intimal flaps, double lumen and intramural haematomas (IMH) is difficult to detect on conventional angiography in most intracranial vertebrobasilar dissecting aneurysms (VBDAs). Our purpose was to assess the value of three-dimensional high-resolution magnetic resonance vessel wall imaging (3D HRMR VWI) for identifying VBDAs.
Methods: Between August 2013 and January 2016, consecutive patients with suspicious VBDAs were prospectively enrolled to undergo catheter angiography and VWI (pre- and post-contrast). The lesion was diagnosed as definite VBDA when presenting direct signs of dissection; as possible when only presenting indirect signs; and as segmental ectasia when there was local dilation and wall thickness similar to adjacent normal artery’s without mural thrombosis.
Results: Twenty-one patients with 27 lesions suspicious for VBDAs were finally included. Based on findings of VWI and catheter angiography, definite VBDA was diagnosed in 25 and 7 lesions (92.6%, vs 25.9%, p = 0.000), respectively; possible VBDA in 0 and 20 (0 vs 74.1%), respectively; and segmental ectasia in 2 and 0 (7.4% vs 0%), respectively. On VWI and catheter angiography, intimal flap was detected in 21 and 7 lesions (77.8% vs 25.9%, p=0.001), respectively; double lumen sign in 18 and 7 (66.7% vs 25.9%, p=0.003), respectively; and IMH sign in 14 and 0 (51.9% vs 0), respectively.
Conclusions: 3D HRMR VWI was superior to catheter angiography in achieving definite diagnosis of intracranial VBDAs with higher rate of detection of direct dissection signs; and allowed a promising way to differentiate between VBDA and segmental ectasia.
Cytokeratin 7-Negative and GATA Binding Protein 3-Negative Breast Cancers: Clinicopathological Features and Prognostic Significance
Authors: Lu Shaolei , Yakirevich Evgeny , Wang Li Juan , Resnick Murray B , Wang Yihong 
Published: July 2019

Abstract
Background: Cytokeratin 7 (CK7) and GATA binding protein 3 (GATA3) are considered as immunohistochemical hallmarks of breast cancers; however, there are breast tumors lacking these markers. Clinicopathological characterization of CK7 negative breast cancer has not been addressed previously and similar studies on GATA3 negative tumors are limited.
Methods: This study included 196 consecutive cases of Nottingham Grade 3 breast cancers with 159 cases of Grade 1 and Grade 2 tumors for comparison. CK7 and GATA3 expression was correlated with patient’s age, histological type, pathological grade and stage, hormone receptor status, molecular subtype and overall survival.
Results: CK7 negativity was seen in 13% of Grade 3, 9% of Grade 2, and 2% of Grade 1 cases (P=0.0457). Similarly, 28% of Grade 3, 5% of Grade 2 and 2 % of Grade 1 cases were GATA3 negative (P<0.0001). CK7 negative tumors did not show association with other clinicopathological parameters. GATA3 negative tumors were enriched in the basal-like molecular subgroup and were associated with negative estrogen receptor (ER) and negative progesterone receptor (PR) statuses. Both CK7 and GATA3 expression showed no association with overall survival in patients with Grade 3 tumor.
Conclusions: More CK7 negative and GATA3 negative tumors were seen in breast cancer of high histologic grade. GATA3 expression was associated with ER status. Lack of CK7 and GATA3 expression in Grade 3 breast cancer was not associated with patient outcome.
Tumour Mutational Burden is Associated with Poor Outcomes that Cannot Be Predicted by Pan-cancer Targeted Sequencing in Diffused Glioma
Authors: Wang Lihong , Ge Jia , Lan Yang , Luo Ying , Tan Yuhuan , Liang Mei , Deng Song , Zhang Xia , Luo Tao 
Published: July 2019

Abstract
Aims

Tumor mutational burden (TMB) is a biomarker for immune checkpoint therapy. The impact of TMB on clinical outcomes and the correlation coefficient between exome sequencing and targeted sequencing in glioma have not yet been explored.

Methods

Somatic mutations in the coding regions of 897 primary gliomas, clinical and RNA-seq information for 654 patients In TCGA dataset were analyzed. Descriptive and correlational analyses were conducted with TMB. Enrichment Map and GSEA was also performed.

Results

TMB was higher for the group of mutant genes that are frequently mutated in glioblastomas (GBMs) and lower for the group of mutant genes that are frequently mutated in lower-grade gliomas (LGGs). Patients with a higher TMB exhibited shorter overall survival. TMB was associated with grade, age, subtype and mutations affecting genomic structure. The signaling pathways of the cell cycle and immune effector processes were enriched in the TMBHigh group. TMB was higher in the mismatch repair (MMR) gene mutant group compared to the wildtype group, but the MMR pathway was enriched in the TMBHigh group of gliomas without mutations in classical MMR genes. The correlation between TMBs calculated through exome sequencing and targeted sequencing was moderate.

Conclusions

TMB is associated with poor outcomes in diffuse glioma. High proliferative activity in the TMBHigh group could account for the shorter survival of these patients. This association was not reflected by a pan-cancer targeted sequencing panel.
Alkaline Comet Assay using the monocytic cell line THP-1
Authors: Neves-Costa Ana , Pedroso Dora , Moita Luis F 
Published: July 2019

Abstract
This protocol details the experimental procedure for performing the comet assay, a very sensitive DNA break assay based on single cell gel electrophoresis.The analysis of DNA strand breaks, both single- and double-strand breaks (SSBs and DSBs, respectively), was performed in immune responsive cells. The cell line used was the human monocytic cell line THP-1, an adherent cell type with many known applications in in vitro studies of innate immunity. The comet assay is a robust procedure that allows the accurate and reproducible quantification of DNA damage. Here we describe not only the comet assay step-by-step protocol, but also some important aspects related to troubleshooting.
Treatment outcome of tuberculosis patients and factors determining treatment outcome at peripheral health settings of Northern Ethiopia: a five year retrospective study
Authors: Abdulkadir Mahmud , Aken Ischa van , Niguse Selam Sahle , Hailekiros Haftamu , Spigt Mark 
Published: July 2019

Abstract
Objective

Evidences of treatment outcome and identifying factors associated with treatment failure through a register based retrospective study have significant contribution in in the improvement of a National Tuberculosis Program. However there is a scarcity of data from peripheral health settings in Ethiopia. Therefore this study is aimed at determining treatment outcome of tuberculosis patients and associated factors.

Results

A total of 3471 patient records were included. More than half, (58%) were males and the mean age was 34 ± 17 years. Majority (43%) had extra-pulmonary TB. From the total TB patients, 18.8% were HIV co infected. The overall treatment success was 89.5%. Being HIV coinfected, pulmonary negative, extra-pulmonary and retreatment case were significantly associated with treatment failure.