bluuebunny/crossref_metadata_2025_split huggingface dataset:
Saccharated ferric oxide attenuates haematopoietic response induced by epoetin beta pegol in patients undergoing haemodialysis
Authors: Iwasaki Takahide , Fujimori Akira , Nakanishi Takeshi , Okada Shioko , Hanawa Nobuto , Hasuike Yukiko , Kuragano Takahiro 
Published: April 2021

Abstract
Background
Decreased erythropoietin levels and impaired iron metabolism due to excessive hepcidin levels are responsible for renal anaemia in patients undergoing haemodialysis. Recently, erythroferrone (ERFE) has been identified as a factor that regulates hepcidin. In addition, fibroblast growth factor 23 (FGF23), which has been recognized as a phosphorus-regulating hormone, appears to be involved in haematopoietic regulation. Clarification of the detailed mechanism of haematopoiesis could lead to the improvement of renal anaemia treatment.

Methods
Epoetin beta pegol (CERA) was administered to patients undergoing haemodialysis at week 0, and the same amount of CERA with saccharated ferric oxide (SFO) was administered at week 4. The changes in haematopoiesis-related biomarkers, including ERFE, intact FGF23 (iFGF23), C-terminal FGF23 (cFGF23), and inflammatory markers, were examined.

Results
Administration of CERA increased ERFE levels, decreased hepcidin levels, and stimulated iron usage for haematopoiesis, leading to an increase in reticulocytes (Ret) and haemoglobin (Hb). Simultaneous administration of SFO with CERA (CERA + SFO) significantly attenuated the responses of ERFE, Ret, and Hb compared with CERA alone. Although iFGF23 levels were not affected by either CERA or CERA + SFO, cFGF23 was significantly elevated from baseline after CERA. Since cFGF23 levels were not affected by CERA + SFO, cFGF23 levels after CERA + SFO were significantly lower than those after CERA alone. The ratio of iFGF23 to cFGF23 (i/cFGF23 ratio) was significantly higher after CERA + SFO than that after CERA alone. In addition, high-sensitivity C-reactive protein (hsCRP) levels were significantly higher after CERA + SFO than after CERA alone.

Conclusion
Administration of SFO suppressed haematopoietic responses induced by CERA. Elevation of i/cFGF23 ratio and hsCRP could account for the inhibitory effects of SFO on haematopoiesis.

Trial registration
This study was registered with the University Hospital Medical Information Network (ID UMIN000016552).
C-terminal and intact FGF23 in kidney transplant recipients and their associations with overall graft survival
Authors: Chu Chang , Elitok Saban , Zeng Shufei , Xiong Yingquan , Hocher Carl-Friedrich , Hasan Ahmed A. , Krämer Bernhard K. , Hocher Berthold 
Published: April 2021

AbstractBackgroundIncreased fibroblast growth factor 23 (FGF23) is a risk factor for mortality, cardiovascular disease, and progression of chronic kidney disease. Limited data exist comparing the association of either c-terminal FGF23 (cFGF23) or intact FGF23 (iFGF23) in kidney transplant recipients (KTRs) with overall (all-cause) graft loss.MethodsWe conducted a prospective observational cohort study in 562 stable kidney transplant recipients. Patients were followed for graft loss and all-cause mortality for a median follow-up of 48 months.ResultsDuring a median follow-up of 48 months, 94 patients had overall graft loss (primary graft loss or death with functioning graft). Both cFGF23 and iFGF23 concentrations were significantly higher in patients with overall graft loss than those without (24.59 [11.43–87.82] versus 10.67 [5.99–22.73] pg/ml;p < 0.0001 and 45.24 [18.63–159.00] versus 29.04 [15.23–60.65] pg/ml;p = 0.002 for cFGF23 and iFGF23, respectively). Time-dependent ROC analysis showed that cFGF23 concentrations had a better discriminatory ability than iFGF23 concentrations in predicting overall (all-cause) graft loss. Cox regression analyses adjusted for risk factors showed that cFGF23 (HR for one unit increase of log transformed cFGF23: 1.35; 95% CI, 1.01–1.79;p = 0.043) but not iFGF23 (HR for one unit increase of log transformed iFGF23: 0.97; 95% CI, 0.75–1.25;p = 0.794) was associated with the overall graft loss.ConclusionElevated cFGF23 concentrations at baseline are independently associated with an increased risk of overall graft loss. iFGF23 measurements were not independently associated with overall graft loss. The cFGF23 ELISA might detect bioactive FGF23 fragments that are not detected by the iFGF23 ELISA.
Increasing false positive diagnoses may lead to overestimation of stroke incidence, particularly in the young: a cross-sectional study
Authors: Appukutty Abhinav J. , Skolarus Lesli E. , Springer Mellanie V. , Meurer William J. , Burke James F. 
Published: April 2021

Abstract
Background
Stroke incidence is reportedly increasing in younger populations, although the reasons for this are not clear. We explored possible reasons by quantifying trends in neurologically focused emergency department (ED) visits, classification of stroke vs. TIA, and imaging use.

Methods
We performed a retrospective, serial, cross-sectional study using the National Hospital Ambulatory Medical Care Survey to examine time trends in age-stratified primary reasons for visit, stroke/TIA diagnoses, and MRI utilization from 1995 to 2000 and 2005–2015.

Results
Five million eight hundred thousand ED visits with a primary diagnosis of stroke (CI 5.3 M–6.4 M) were represented in the data. The incidence of neurologically focused reason for visits (Neuro RFVs) increased over time in both the young and in older adults (young: + 111 Neuro RFVs/100,000 population/year, CI + 94 − + 130; older adults: + 70 Neuro RFVs/100,000 population/year, CI + 34 − + 108). The proportion of combined stroke and TIA diagnoses decreased over time amongst older adults with a Neuro RFV (OR 0.95 per year, p < 0.01, CI 0.94–0.96) but did not change in the young (OR 1.00 per year, p = 0.88, CI 0.95–1.04). Within the stroke/TIA population, no changes in the proportion of stroke or TIA were identified. MRI utilization rates amongst patients with a Neuro RFV increased for both age groups.

Conclusions
We found, but did not anticipate, increased incidence of neurologically focused ED visits in both age groups. Given the lower pre-test probability of a stroke in younger adults, this suggests that false positive stroke diagnoses may be increasing and may be increasing more rapidly in the young than in older adults.
KLF5-mediated Eppk1 expression promotes cell proliferation in cervical cancer via the p38 signaling pathway
Authors: Ma Dong , Pan Zhe , Chang Quan , Zhang Jin-jin , Liu Xiao , Hua Na , Li Guo-Hua 
Published: April 2021

Abstract
Background
Epiplakin1 (Eppk1) is part of epidermal growth factor (EGF) signal and takes part in reorganization of cytoskeleton and cell proliferation. However, the role of Eppk1 in cervical cancer (CC) remains unknown.

Methods
To express Eppk1 and KLF5 and their correlation, we used RNA-sequence, RT-qPCR, TCGA database and immunofluorescence staining in vitro and in different pathological cervical tissues. In CC cell lines, we tested adenovirus-mediated over expression or knockdown of KLF5 and siRNA-mediated knockdown of Eppk1 and a suiting assessment of cell proliferation and cell signaling by western blot and CCK8 tests. We studied the mechanism by which KLF5 regulates Eppk1 expression by reporter gene test and chromatin immunoprecipitation test.

Results
Eppk1 expression promoted in CC tissues and cell lines compared with increased KLF5 expression. The results of immunofluorescence staining further showed the increased co-expression of Eppk1 and KLF5 correlated substantially with tumorigenesis in cervical tissues. Overexpression of KLF5 significantly increased Eppk1 expression at transcription and translation levels. Conversely, the knockdown of KLF5 by siRNA against KLF5 decreased Eppk1 expression. Mechanically, KLF5 activated Eppk1 transcription by direct binding to the Eppk1 promoter. Gain- and loss-of-function experiments reported that KLF5 promoted cell proliferation in Hela partly dependent on Eppk1 upregulation. Besides, KLF5-mediated activation of p38 signaling significantly decreased after Eppk1 knockdown compared with decline of proliferation, suggesting that Eppk1 lies upstream of p38 signaling affecting cell proliferation. Finally, Eppk1 expression is positively correlated with tumor size in clinicopathological features of CC.

Conclusions
Eppk1 may be an effective therapeutic target for affecting p38 signaling pathway and cell proliferation in cervical cancer.
POU2F2 promotes the proliferation and motility of lung cancer cells by activating AGO1
Authors: Luo Ronggang , Zhuo Yi , Du Quan , Xiao Rendong 
Published: April 2021

Abstract
Background
To detect and investigate the expression of POU domain class 2 transcription factor 2 (POU2F2) in human lung cancer tissues, its role in lung cancer progression, and the potential mechanisms.

Methods
Immunohistochemical (IHC) assays were conducted to assess the expression of POU2F2 in human lung cancer tissues. Immunoblot assays were performed to assess the expression levels of POU2F2 in human lung cancer tissues and cell lines. CCK-8, colony formation, and transwell-migration/invasion assays were conducted to detect the effects of POU2F2 and AGO1 on the proliferaion and motility of A549 and H1299 cells in vitro. CHIP and luciferase assays were performed for the mechanism study. A tumor xenotransplantation model was used to detect the effects of POU2F2 on tumor growth in vivo.

Results
We found POU2F2 was highly expressed in human lung cancer tissues and cell lines, and associated with the lung cancer patients’ prognosis and clinical features. POU2F2 promoted the proliferation, and motility of lung cancer cells via targeting AGO1 in vitro. Additionally, POU2F2 promoted tumor growth of lung cancer cells via AGO1 in vivo.

Conclusion
We found POU2F2 was highly expressed in lung cancer cells and confirmed the involvement of POU2F2 in lung cancer progression, and thought POU2F2 could act as a potential therapeutic target for lung cancer.
Modified team-based and blended learning perception: a cohort study among medical students at King Saud University
Authors: Albarrak Ahmed I. , Zakaria Nasriah , Almulhem Jwaher , Khan Samina A. , Karim Norshahriza Abdul 
Published: April 2021

Abstract
Background & Objective
Medical schools have evolved toward competency-based education and active learner-centered strategies. Medical informatics course was introduced in 2011 in the 3rd year at the College of Medicine (CoM), King Saud University (KSU), to enhance future medical graduates with technological and information competencies. Modified team-based learning and blended learning were emphasized using face-to-face lectures, various e-learning technologies, workshop and seminars. The current study’s main objective was to assess students’ perceptions towards blended and modified team-based learning at the CoM in KSU.

Methods
A survey was distributed to medical students in three consecutive years: 2017–2019. The survey contains items regarding student perception of various types of blended learning techniques applied in the course. The survey was administered using i-Clicker; an interactive device that enables students to answer survey questions. Descriptive statistics were used to examine the perception of students on these blended learning dimensions investigated.

Results
Seven-hundred and one student responded to the questionnaire (male; 69.5%, female 30.5%). Out of which, 59.1% of students found team interactions positively supported discussions and asked questions freely, and 48.1% expressed that working in groups facilitated their learning process. However, 56.0% of students chose face-to-face lectures as the most preferred class activities followed by discussion 23.8%. More than 78% of participants agree that online quizzes are good experience and enjoyable. Grade center where students can check for marks and attendance also received high perception (66.3%).

Conclusion
Introducing modified team-based and blended-learning are considered challenging, and therefore, investigating their perceptions can provide useful insights into how these methods could be used more effectively. The blended-learning technique is highly essential in teaching medical informatics to overcome challenges faced due to a large number of students and the need for various exposures to reach the course’s learning goals. Moreover, it is noticed that students were engaged in face-to-face and online activities, furthermore, modified team-based learning reported facilitating learning and asking questions without embarrassment.
Stacked LSTM based deep recurrent neural network with kalman smoothing for blood glucose prediction
Authors: Rabby Md Fazle , Tu Yazhou , Hossen Md Imran , Lee Insup , Maida Anthony S. , Hei Xiali 
Published: April 2021

Abstract
Background
Blood glucose (BG) management is crucial for type-1 diabetes patients resulting in the necessity of reliable artificial pancreas or insulin infusion systems. In recent years, deep learning techniques have been utilized for a more accurate BG level prediction system. However, continuous glucose monitoring (CGM) readings are susceptible to sensor errors. As a result, inaccurate CGM readings would affect BG prediction and make it unreliable, even if the most optimal machine learning model is used.

Methods
In this work, we propose a novel approach to predicting blood glucose level with a stacked Long short-term memory (LSTM) based deep recurrent neural network (RNN) model considering sensor fault. We use the Kalman smoothing technique for the correction of the inaccurate CGM readings due to sensor error.

Results
For the OhioT1DM (2018) dataset, containing eight weeks’ data from six different patients, we achieve an average RMSE of 6.45 and 17.24 mg/dl for 30 min and 60 min of prediction horizon (PH), respectively.

Conclusions
To the best of our knowledge, this is the leading average prediction accuracy for the ohioT1DM dataset. Different physiological information, e.g., Kalman smoothed CGM data, carbohydrates from the meal, bolus insulin, and cumulative step counts in a fixed time interval, are crafted to represent meaningful features used as input to the model. The goal of our approach is to lower the difference between the predicted CGM values and the fingerstick blood glucose readings—the ground truth. Our results indicate that the proposed approach is feasible for more reliable BG forecasting that might improve the performance of the artificial pancreas and insulin infusion system for T1D diabetes management.
Protocol for a mixed methods exploratory investigation into the role and contribution of the healthcare assistant in out-of-hours palliative care
Authors: Hasson Felicity , McIlfatrick Sonja , Payne Sheila , Slater Paul , Finlay Dori-Anne , McConnell Tracey , Fee Anne 
Published: April 2021

Abstract
Background
Most people spend their last year of life at home, with many wishing to die there, but patients may need access to care after hours. Out-of-hours palliative care is delivered by multi-disciplinary teams including Health Care Assistants (HCA). However, little is known about the role, contribution and impact Health Care Assistants have on out-of-hours palliative care services. The aim of this study is to examine the Health Care Assistant role, contribution and impact on service delivery and patient care in out-of-hours community palliative care provided by hospice organisations.

Methods and analysis
A mixed methods exploratory study consisting of four phases. Phase one involves a scoping review to systematically map and identify gaps in policy and literature on the HCA role in out-of-hours palliative care. In phase two, all United Kingdom hospices will be invited to participate in an online census to enable the development of a typology of out-of-hours services and the contribution of the Health Care Assistant. During phase three organisational case studies representing different service types will collect information from Health Care Assistants, patients, caregivers and service managers to gather qualitative and quantitative data about out-of-hours service provision and the Health Care Assistant role. Finally, phase four will synthesize and refine results through online focus groups.

Ethics and dissemination
Ethical approval has been obtained for phase two through Ulster University Research Governance Filter Committee, Nursing and Health Research. Findings will be disseminated through practitioner and/or research journals, conferences, and social media.
The cost-effectiveness of Cochlear implants in Swedish adults
Authors: Gumbie Mutsa , Olin Emma , Parkinson Bonny , Bowman Ross , Cutler Henry 
Published: April 2021

AbstractBackgroundResearch has shown unilateral cochlear implants (CIs) significantly improve clinical outcomes and quality of life in adults. However, only 13% of eligible Swedish adults currently use a unilateral CI. The objective was to estimate the cost-effectiveness of unilateral CIs compared to a hearing aid for Swedish adults with severe to profound hearing loss.MethodsA Markov model with a lifetime horizon and six-month cycle length was developed to estimate the benefits and costs of unilateral CIs from the Swedish health system perspective. A treatment pathway was developed through consultation with clinical experts to estimate resource use and costs. Unit costs were derived from the Swedish National Board of Health and Welfare and the Swedish Association of Local Authorities and Regions. Health outcomes were reported in terms of Quality Adjusted Life Years (QALYs).ResultsUnilateral CIs for Swedish adults with severe to profound hearing loss are likely to be deemed cost-effective when compared to a hearing aid (SEK 140,474 per QALY gained). The results were most sensitive to the age when patients are implanted with a CI and the proportion of patients eligible for CIs after triage.ConclusionsAn increase in the prevalence of Swedish adults with severe to profound hearing loss is expected as the population ages. Earlier implantation of unilateral CIs improves the cost-effectiveness among people eligible for CIs. Unilateral CIs are an efficacious and cost-effective option to improve hearing and quality of life in Swedish adults with severe to profound hearing loss.
Urgent care center wait times increase for COVID-19 results in August 2020, with rapid testing availability limited
Authors: Yousman Laurie C , Khunte Akshay , Hsiang Walter , Jain Siddharth , Forman Howard , Wiznia Daniel 
Published: April 2021

Abstract
Background
In a response to the pandemic, urgent care centers (UCCs) have gained a critical role as a common location for COVID-19 testing. We sought to characterize the changes in testing accessibility at UCCs between March and August 2020 on the basis of testing availability (including rapid antigen testing), wait time for test results, cost of visits, and cost of tests.

Methods
Data were collected using a secret shopper methodology. Researchers contacted 250 UCCs in 10 states. Investigators used a standardized script to survey centers on their COVID-19 testing availability and policies. UCCs were initially contacted in March and re-called in August. T-tests and chi-square tests were conducted to identify differences between March and August data and differences by center classification.

Results
Our results indicate that both polymerase chain reaction (PCR) tests to detect COVID-19 genetic material and rapid antigen COVID-19 tests have increased in availability. However, wait times for PCR test results have significantly increased to an average of 5.79 days. Additionally, a high proportion of UCCs continue to charge for tests and visits and no significant decrease was found in the proportion of UCCs that charge for COVID-19 testing from March to August. Further, no state reported a majority of UCCs with rapid testing available, indicating an overall lack of rapid testing.

Conclusions
From March to August, COVID-19 testing availability gradually improved. However, many barriers lie in access to COVID-19 testing, including testing costs, visit costs, and overall lack of availability of rapid testing in the majority of UCCs. Despite the passage of the CARES Act, these results suggest that there is room for additional policy to improve accessibility to testing, specifically rapid testing.
The effects of MEX3A knockdown on proliferation, apoptosis and migration of osteosarcoma cells
Authors: Wang Bangmin , Hong Zheping , Zhao Chen , Bi Qing , Yuan Junhui , Chen Jihang , Shen Yi 
Published: April 2021

AbstractBackgroundOsteosarcoma is an aggressive malignant tumor which has attracted worldwide attention. MEX3A may be associated with tumors while has not yet seen its coverage on osteosarcoma. Herein, this study was to investigate the correlation between MEX3A and the progression of osteosarcoma.MethodsFirstly, we determined that expression of MEX3A was significantly higher in osteosarcoma tissues than that in marginal bone by immunohistochemical staining. Additionally, MEX3A expression was downregulated by the RNAi‐mediated knockdown. The functions of MEX3A knockdown on proliferation, apoptosis, cell cycle, migration was assessed by MTT assay, flow cytometry, wound-healing assay and Transwell assay, respectively. Knockdown of MEX3A resulted in suppressing cell proliferation, increasing cell apoptosis, inducing the G2 phase cell cycle arrest, and attenuating cellular migration. Furthermore, mouse xenograft model confirmed inhibitory effects of MEX3A knockdown on osteosarcoma formation.ResultsThe preliminary exploration on the molecular mechanism of MEX3A in osteosarcoma cells showed that the induction of apoptosis needs the participation of a series of apoptosis- associated factors, such as upregulation of Caspase 3, Caspase 8 and HSP60, downregulation of HSP27 and XIAP.ConclusionsIn summary, these findings predicated that therapy directed at decreasing MEX3A expression is a potential osteosarcoma treatment.
Corneal confocal microscopy differentiates inflammatory from diabetic neuropathy
Authors: Fleischer Michael , Lee Inn , Erdlenbruch Friedrich , Hinrichs Lena , Petropoulos Ioannis N. , Malik Rayaz A. , Hartung Hans-Peter , Kieseier Bernd C. , Kleinschnitz Christoph , Stettner Mark 
Published: April 2021

Abstract
Background
Immune-mediated neuropathies, such as chronic inflammatory demyelinating polyneuropathy (CIDP) are treatable neuropathies. Among individuals with diabetic neuropathy, it remains a challenge to identify those individuals who develop CIDP. Corneal confocal microscopy (CCM) has been shown to detect corneal nerve fiber loss and cellular infiltrates in the sub-basal layer of the cornea. The objective of the study was to determine whether CCM can distinguish diabetic neuropathy from CIDP and whether CCM can detect CIDP in persons with coexisting diabetes.

Methods
In this multicenter, case-control study, participants with CIDP (n = 55) with (n = 10) and without (n = 45) diabetes; participants with diabetes (n = 58) with (n = 28) and without (n = 30) diabetic neuropathy, and healthy controls (n = 58) underwent CCM. Corneal nerve fiber density (CNFD), corneal nerve fiber length (CNFL), corneal nerve branch density (CNBD), and dendritic and non-dendritic cell density, with or without nerve fiber contact were quantified.

Results
Dendritic cell density in proximity to corneal nerve fibers was significantly higher in participants with CIDP with and without diabetes compared to participants with diabetic neuropathy and controls. CNFD, CNFL, and CNBD were equally reduced in participants with CIDP, diabetic neuropathy, and CIDP with diabetes.

Conclusions
An increase in dendritic cell density identifies persons with CIDP. CCM may, therefore, be useful to differentiate inflammatory from non-inflammatory diabetic neuropathy.